| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The neutral endopeptidase inhibitor phosphoramidon ( 1 microM ) increased the potency of ANF ( 5 27 ) in both epithelium intact and epithelium denuded guinea pig tracheal rings . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| A novel small linear C atrial natriuretic factor receptor ligand [ C ANF ( 11 15 ) ] and phosphoramidon ( PHO ) were used to determine the effects of C ANF receptor blockade alone , or in combination with inhibition of neutral endopeptidase ( NEP ) , on the pharmacokinetics and metabolism of ANF in the rat . ^^^ High performance liquid chromatography analysis revealed that C ANF ( 11 15 ) inhibited the delayed appearance of free 125I and [ 125I ] monoiodotyrosine but had no effect on the small proportion of NEP metabolites in plasma . ^^^ The combination of C ANF ( 11 15 ) and PHO further delayed the appearance of small metabolites , abolished the appearance of NEP metabolites , and markedly prolonged the permanence of intact 125I ANF ( 1 28 ) in plasma . ^^^ The results demonstrate that C ANF receptor blockade by C ANF ( 11 15 ) impairs clearance and metabolism of ANF , an effect which is synergistically potentiated by concomitant inhibition of NEP . ^^^ C ANF ( 11 15 ) alone or in combination with NEP inhibitors may be a potentially useful therapeutic tool in the treatment of cardiovascular and renal diseases . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Effects of neutral endopeptidase inhibition with candoxatrilat and of ANF C receptor blockade . ^^^ Our studies indicate that neutral endopeptidase and ANF C receptors are both major , and approximately equal , clearance mechanisms for 125I ANF , together accounting for at least 75 % of the total clearance of this peptide in the rat . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Prior treatment of rats with SQ 28 , 603 , a specific neutral endopeptidase ( NEP ; EN 3 . 4 . 24 . 11 ) inhibitor , was without significant effect on the metabolic clearance of urodilatin , whereas it decreased the clearance of ANF by 65 % . ^^^ Pharmacokinetics of ANF and urodilatin during cANF receptor blockade and neutral endopeptidase inhibition . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Recently , inhibitors of the ANF degrading enzyme , neutral endopeptidase , and of the ANF `` clearance ' ' receptor have enhanced the antihypertensive actions of endogenous or exogenously administered ANF . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase ( NEP ) , an enzyme of which ANF is a specific substrate in the kidney , is expressed at the cell surface . ^^^ Degradation of ANF occurs via two different ways , its conversion into inactive peptides by NEP and its internalization after binding to C receptors . . ^^^ Neutral endopeptidase ( NEP ) , an enzyme of which ANF is a specific substrate in the kidney , is expressed at the cell surface . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| By contrast , ANF fragments produced by enkephalinase ( EC 3 . 4 24 . 11 , membrane metalloendopeptidase ) were less potent or even inactive in competing with [ 125I ] rANF . ^^^ These data confirm by a novel approach that enkephalinase plays a key role in the inactivation of circulating ANF . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Thiorphan , a potent inhibitor of enkephalinase ( membrane metalloendopeptidase , atriopeptidase , EC 3 . 4 . 24 . 11 ) enhanced markedly ( +214 % ) and prolonged the rise in plasma atrial natriuretic factor ( ANF ) immunoreactivity in anesthetized rats submitted to acute extracellular volume expansion obtained through i . v . injection of a Ringer ' s solution . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase 3 . 4 . 24 . 11 ( NEP ) has been identified as the major atrial natriuretic factor ( ANF ) degrading enzyme in rat kidney , therefore , suggesting a possible role for this enzyme in blood volume and pressure regulation . ^^^ Neutral endopeptidase 3 . 4 . 24 . 11 ( NEP ) has been identified as the major atrial natriuretic factor ( ANF ) degrading enzyme in rat kidney , therefore , suggesting a possible role for this enzyme in blood volume and pressure regulation . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The neutral endopeptidase 24 . 11 ( NEP ) has been shown to inactivate the atrial natriuretic factor ( ANF ) by opening the ring structure . ^^^ To document the role of NEP in the metabolic fate of ANF in vivo , the effects of an infusion of thiorphan ( 25 micrograms / min / kg ) , a specific NEP inhibitor , on the kinetics and metabolism of endogenous ANF were studied in conscious rabbits . ^^^ These results support a role for NEP in the regulation of endogenous ANF plasma levels . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Inhibition of neutral endopeptidase activity by phosphoramidon ( 10 ( 6 ) M ) or thiorphan ( 10 ( 6 ) M ) potentiated the effect of ANF so that the dose response curve for ANF was shifted to lower concentrations by approximately 0 . 5 log units ( P less than 0 . 05 , in each case ) . ^^^ These results suggest that ANF inhibits ciliary motility presumably through a guanylate cyclase dependent regulatory pathway and that neutral endopeptidase may play a role in modulating the ANF effect on airway mucociliary transport function . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| C ANF ( 4 23 ) and neutral metalloendopeptidase ( NEP ) inhibitors have been shown to prevent ANF metabolism and lower blood pressure presumably by the accumulation of ANF in the circulation . ^^^ In the present study , we examined the interaction between C ANF ( 4 23 ) and SCH 34826 , an inhibitor of NEP , and ensuing effects on blood pressure , excretion of urine and sodium , and cGMP in the plasma and urine in conscious DOCA salt hypertensive rats . ^^^ It is suggested that the greater blood pressure and renal responses to a combination of SCH 34826 and C ANF than either agent alone reflect greater accumulation of endogenous ANF due to concomitant inhibition of both receptor mediated clearance and NEP . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The role of C atrial natriuretic factor ( ANF ) receptors and neutral endopeptidase ( NEP ) in the pharmacokinetics and hydrolysis of 125I labeled ANF was evaluated in rats by using C ANF and SCH 39370 to block the nonenzymatic and enzymatic pathways , respectively . ^^^ SCH 39370 systemically inhibits ANF hydrolysis ; the resulting increase in ANF , however , is masked by the great capacity of ANF clearance receptors but can be revealed with excess C ANF , suggesting that the plasma ANF concentrations are determined by the interplay of the C ANF receptor and NEP systems . . ^^^ Influence of C ANF receptor and neutral endopeptidase on pharmacokinetics of ANF in rats . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| We examined the acute effects of sinorphan , an inhibitor of enkephalinase , on plasma atrial natriuretic factor ( ANF ) and urinary sodium excretion in cirrhotic patients with ascites . ^^^ Sinorphan , at a dose of 100 mg , inhibited 70 % of plasma enkephalinase activity 60 min after ingestion and elicited simultaneously an increase in plasma ANF and cGMP levels 1 . 8 and 1 . 5 times basal values , respectively . ^^^ Therefore , enkephalinase inhibition transiently increases sodium urinary excretion in cirrhotic patients with ascites via a mechanism that is likely to imply reduction of ANF catabolism . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The effects of a clearance receptor ligand Arg Ser Ser Cys Phe Gly Gly Arg Ile Asp Arg Ile Gly Ala Cys NH 2 with a disulfide bridge between the two cycteines [ C ANF ( 4 23 ) ] and the potent neutral endopeptidase ( NEP ) inhibitor SQ 28 , 603 on mean arterial pressure ( MAP ) , plasma atrial natriuretic factor ( ANF ) concentration and renal excretion of sodium and cyclic GMP were determined in conscious deoxycorticosterone acetate / salt hypertensive rats and normotensive rats . ^^^ Finally , the in vitro hydrolysis of C ANF ( 4 23 ) by NEP was prevented by SQ 28 , 603 , indicating that inhibition of NEP may protect peptides recognized by the clearance receptors as well as the biological receptors for ANF . ^^^ Therefore , the additive effects of C ANF ( 4 23 ) and SQ 28 , 603 may be due to blockade of separate pathways which inactivate ANF or to the inhibition of C ANF ( 4 23 ) degradation by NEP . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| A new pharmacological approach in this area is the development of neutral endopeptidase inhibitors , which prolong the half life of endogenous ANF and potentiate its effects . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The data assembled to date indicate that NEP inhibition elicits significant ANF like effects in animals and man . ^^^ SCH 34826 : an overview of its profile as a neutral endopeptidase inhibitor and ANF potentiator . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| ANF , ANF 7 28 and atriopeptins ( AP 1 , AP 2 and AP 3 ) ( 10 ( 11 ) to 3 10 10 ( 7 ) M ) induce a relaxant response on the guinea pig isolated trachea , which is partially potentiated by the enkephalinase inhibitor thiorphan 10 ( 5 ) M but is unmodified by epithelium removal . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The neutral endopeptidase 24 . 11 ( NEP ) was shown to degrade atrial natriuretic factor ( ANF ) in kidney membranes . ^^^ An infusion of Thiorphan ( 25 micrograms / min / kg 10 90 min ) , a specific NEP inhibitor , induced an increase in plasma ANF ( 65 + / 26 to 163 + / 52 pg / ml ) , plasma renin activity and in norepinephrine concentrations at 50 minutes of infusion in conscious rabbits . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The present studies were designed to determine the action of neutral endopeptidase inhibition ( NEP 1 ) , an inhibitor of the degradation of atrial natriuretic factor ( ANF ) , in congestive heart failure ( CHF ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The effects of neutral endopeptidase inhibition have been studied in seven sodium replete sheep using SCH 39370 , a specific and potent inhibitor of neutral endopeptidase , in the presence or absence of exogenous hormone [ rat ANF ( 101 126 ) , 2 . 4 pmol / kg / min for 2 hours ] . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Atrial natriuretic factor ( ANF ) is a peptide hormone of cardiac origin elevated in acute congestive heart failure ( CHF ) , which is degraded by the enzyme neutral endopeptidase 24 . 11 ( NEP ) . ^^^ NEP inhibition ( NEPI ) abolished both the clearance and extraction of plasma ANF across the lung in CHF . ^^^ This study supports an important role for NEP in the pulmonary and urinary metabolism of endogenous ANF during acute CHF . . ^^^ NEPI prevented the decrease in the urinary clearance of ANF , and enhanced the renal response to endogenous ANF , independent of further increases in plasma ANF during CHF . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Angiotensin converting enzyme ( ACE ) and enkephalinase , two cell surface metallopeptidases , are responsible for angiotensin 2 formation and atrial natriuretic factor ( ANF ) degradation , respectively , and thereby play a critical role in the metabolism of hormonal peptides exerting essentially opposite actions in cardiovascular regulations . ^^^ In rodents , low doses of these mixed inhibitors exert typical actions of ACE inhibitors i . e . , prevention of angiotensin 1 induced hypertension as well as of enkephalinase inhibitors i . e . , protection from 125I ANF degradation or enhancement of diuresis and natriuresis following acute extracellular volume expansion . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Oral pretreatment with acetorphan , a potent enkephalinase inhibitor resulted in a marked increase in the amount of intact 125I ANF ( 6 fold ) , TCA precipitated ( 5 fold ) and membrane bound radioactivity ( 4 fold ) in the kidney ; the total kidney radioactivity was enhanced by approximately 2 fold . ^^^ The crucial role of enkephalinase in ANF inactivation in vivo suggests that inhibitors of this peptidase could be used in a novel therapeutic approach to cardiovascular or renal diseases by protecting endogenous ANF . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| These various observations suggest that enkephalinase inhibitors protect endogenous ANF from degradation and thereby enhance the typical renal effects of the hormone . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Enkephalinase ( EC 3 . 4 . 24 . 11 ) inhibitors : protection of endogenous ANF against inactivation and potential therapeutic applications . ^^^ The critical role played by enkephalinase ( membrane metalloendopeptidase , EC 3 . 4 . 24 . 11 ) in ANF inactivation was deduced from the effects of inhibitors . ^^^ Enkephalinase ( EC 3 . 4 . 24 . 11 ) inhibitors : protection of endogenous ANF against inactivation and potential therapeutic applications . ^^^ In addition , enkephalinase inhibitors increase by two to three fold the circulating level of endogenous ANF , even when the latter is already markedly elevated , such as in patients with chronic heart failure . ^^^ Finally , enkephalinase inhibitors induce a series of ANF like responses such as natriuresis , diuresis or increase in cGMP excretion which are attributable to the hormone . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Inhibition of the enzyme neutral metalloendopeptidase ( NEP ) potentiates responses to atrial natriuretic factor ( ANF ) and elicits reductions in blood pressure in deoxycorticosterone acetate sodium ( DOCA Na ) hypertensive rats . ^^^ The present study evaluated the role of ANF and bradykinin in the antihypertensive response to NEP inhibition through the use of antibodies and antagonists , respectively . ^^^ In addition , the pharmacokinetic mechanism by which NEP inhibition interferes with ANF metabolism was explored . ^^^ The antihypertensive response to the NEP inhibitors SCH 34826 and 42495 was abruptly reversed by an intravenous injection of a polyclonal antiserum to ANF . ^^^ The NEP inhibitor SCH 39370 significantly delayed the disappearance of trichloroacetic acid ( TCA ) precipitable radioactivity and the appearance of TCA soluble radioactivity in plasma following an intravenous bolus dose of 125I ANF ( 99 126 ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Atrial natriuretic factor ( ANF ) is degraded by neutral endopeptidase . ^^^ We hypothesized that neutral endopeptidase inhibition ( NEP 1 ) increases sodium excretion and that this effect would be potentiated in the presence of an isolated increase in intrarenal ANF . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The endopeptidase EC 3 . 4 . 24 . 11 ( atriopeptidase ) degrades atrial natriuretic factor ( ANF ) . ^^^ Intravenous administration of UK 69 , 578 ( 0 . 025 to 10 . 0 mg / kg ) , a new specific atriopeptidase inhibitor , in 16 normal volunteers produced a two to three fold rise in endogenous ANF . ^^^ We conclude that inhibition of the endopeptidase EC 3 . 4 . 24 . 11 in humans elevates endogenous ANF and causes a natriuresis and may offer a novel therapeutic approach to the treatment of hypertension and cardiac failure . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Atrial natriuretic factor ( ANF ) is a peptide hormone secreted by the heart that is degraded in vivo by endopeptidase 24 : 11 ( atriopeptidase ) . ^^^ UK 69 , 578 is a novel atriopeptidase inhibitor that raises plasma levels of ANF in animals and normal volunteers , with associated diuresis and natriuresis . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| We compared the relative potencies of sinorphan and retorphan , the S and R enantiomers of acetorphan a potent inhibitor of enkephalinase ( EC 3 . 4 . 34 . 11 ) , to inhibit membrane metalloendopeptidase in vivo and to protect exogenous and endogenous ANF after oral administration . ^^^ These data indicate that , in humans as in rodents , enkephalinase plays a crucial role in the inactivation of ANF , its partial inhibition in vivo being accompanied by a significant protection of the exogenous or endogenous hormone as well as by typical ANF like responses . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| In addition , linear ANF markedly inhibited the degradation of 125I ANF in the incubation medium of epithelial and mesangial cells , whereas thiorphan , an inhibitor of enkephalinase , was inactive . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Major mechanisms for ANF clearance are uptake by clearance receptors and degradation by an endoprotease ( EC 3 . 4 . 24 . 11 . ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase , an ectoenzyme present in different tissues and particularly in the kidney is also capable to cleave ANF in unefficient peptide . ^^^ The blockade of ANF metabolism by clearance receptor antagonists and neutral endopeptidase inhibitor potentializes the biological effect of exogenous and endogenous ANF particularly on the renal function . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| In addition to enkephalins , NEP cleaves kinins , chemotactic peptide , atrial natriuretic factor ( ANF ) , and substance P in vivo . ^^^ Because of the possible involvement of NEP in the metabolism of opioid peptides and the cardiac hormone ANF , orally active inhibitors have been synthesized . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| We have assessed the role of enkephalinase ( membrane metallo endopeptidase , EC 3 . 4 . 24 . 11 ) in the in vivo inactivation of ANF in mice and healthy human volunteers by evaluating the effects of acetorphan , a potent inhibitor . ^^^ Oral administration of acetorphan elicited a lasting elevation of plasma ANF like immunoreactivity , with a time course parallel to that of the inhibition of plasma enkephalinase activity . ^^^ These results indicate that enkephalinase plays a critical role in ANF degradation in vivo and that its inhibition enhances the levels of circulating endogenous ANF , which , in turn , results in diuresis and natriuresis . ^^^ Enkephalinase inhibition may constitute another therapeutic approach to the treatment of cardiovascular diseases , such as congestive heart failure or essential hypertension , on which ANF is postulated to have a beneficial effect . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| UK 69 , 578 , a novel inhibitor of EC 3 . 4 . 24 . 11 which increases endogenous ANF levels and is natriuretic and diuretic . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| These findings are consistent with the action of endopeptidase EC 3 . 4 . 24 . 11 , which may play an important part in the biological inactivation of ANF . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| We evaluated the effect of NEP inhibition with SCH 39370 on the inactivation of atrial natriuretic factor ( ANF ) and on cardiovascular function in rats . ^^^ SCH 39370 effectively prevented in vitro degradation of ANF ( 99 126 ) by a purified rabbit kidney NEP . ^^^ The results suggest that NEP can play a role in ANF disposition in vivo and that potentiation of the biological activities of high doses of ANF by SCH 39370 may be consequent to its inhibitory effect on ANF degradation . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Blockade of atrial natriuretic factor ( ANF ) degradation by specific neutral endopeptidase ( NEP ) inhibitors may be useful in treatment of hypertension because of the potential diuretic , natriuretic , and arterial pressure ( AP ) lowering effects . ^^^ To test this possibility , we examined the effects of chronic oral treatment with the NEP inhibitor SCH 42495 on BP , diuresis , natriuresis , plasma ANF , cyclic GMP , and the renin angiotensin system ( RAS ) in conscious unrestrained spontaneously hypertensive rats ( SHR ) and compared them with the effects induced by the angiotensin converting enzyme ( ACE ) inhibitor spirapril ( SPIR ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Urodilatin is an amino terminally extended form of atrial natriuretic factor ( ANF ) which is resistant to enzymatic cleavage by renal neutral endopeptidase ( NEP : EC 3 . 4 . 24 . 11 ) . ^^^ This study does not support the hypothesis that changes in NEP activity contribute to the modulation of the natriuretic response to ANF which is observed with modification of sodium status . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Recognizing that neutral endopeptidase 24 . 11 degrades ANF and may be enhanced in CHF , we hypothesized that chronic neutral endopeptidase inhibition ( NEP 1 ) would potentiate renal responses to exogenous ANF and alter the temporal evolution of sodium retention in evolving CHF by potentiation of increased endogenous ANF . ^^^ CONCLUSIONS : Enzymatic degradation by neutral endopeptidase limits local renal responses to increases in endogenous and exogenous ANF in CHF independent of changes in systemic hemodynamics or augmented plasma concentrations of ANF . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The aim of the study was to compare , in a rat model of congestive heart failure , the effect of captopril , a selective angiotensin converting enzyme ( ACE ; EC 3 . 4 . 15 . 1 ) inhibitor , to that of alatriopril , a mixed inhibitor of ACE and atriopeptidase ( EC 3 . 4 . 24 . 11 ) , an enzyme implicated in the degradation of atrial natriuretic factor ( ANF ) . ^^^ In contrast , plasma ANF level was significantly reduced after captopril but not after alatriopril treatment , a difference that probably reflects the protection of endogenous ANF in circulation resulting from atriopeptidase inhibition . ^^^ These data suggest that enhancement of ANF levels in circulation via atriopeptidase inhibition magnifies the capacity of ACE inhibitors to prevent cardiac hypertrophy , and they show the potential therapeutic value of mixed ACE atriopeptidase inhibitors in congestive heart failure . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| OBJECTIVE : The aim was to investigate whether infusion of either atrial natriuretic factor ( ANF , 800 ng . h 1 . rat 1 ) or a specific inhibitory of neutral endopeptidase 24 . 11 ( NEI , UK 73 , 967 , 5 . 4 mg . kg 1 . d 1 ) can influence the reversal of the pulmonary vascular remodelling produced by exposure to hypoxia . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Since ANF discovery by De Bold in 1981 , progress have been accomplished including the description of a family of natriuretic peptides derived from ANF and therapeutic trials of neutral endopeptidase inhibitors , a new pharmacologic class of diuretics . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase inhibitors ( NEP ) inhibit ANF degradation , increase thus its plasma level and in cardiac weakntlakess have a marked diuretic and natriuretic effect . ^^^ Neutral endopeptidase inhibitors ( NEP ) inhibit ANF degradation , increase thus its plasma level and in cardiac weakntlakess have a marked diuretic and natriuretic effect . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Candoxatrilat is a potent and selective inhibitor of neutral endopeptidase ( EC 3 . 4 . 24 . 11 ) , the enzyme responsible for the degradation of atrial natriuretic factor ( ANF ) . ^^^ The results presented suggest that plasma ANF levels and volume status modulate responses to neutral endopeptidase inhibition . ^^^ The development of the neutral endopeptidase inhibitor , candoxatrilat , provides the opportunity to exploit endogenous ANF effectively in disease states with elevated ANF . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| ANF metabolism occurs via degradation by neutral endopeptidase 24 . 11 and binding to the ANF clearance receptor ( ANFR C ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Inhibitors of the zinc protease neutral endopeptidase ( NEP , EC 3 . 4 . 24 . 11 ) offer significant therapeutic interest as antihypertensives due to their ability to potentiate the biological action of the circulating natriuretic hormone ANF ( atrial natriuretic factor ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Alatriopril is a dual inhibitor of two cell surface metallopeptidases which play important roles in the regulation of arterial blood pressure and renal function : the angiotensin 1 converting enzyme ( ACE ) which catalyses transformation of angiotensin 1 to angiotensin 2 , and the neutral endopeptidase ( NEP ; EC 3 . 4 . 24 . 11 ; atriopeptidase ) , responsible for the degradation of the atrial natriuretic factor ( ANF ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| It is concluded that the antihypertensive action of SCH 32615 and low doses of phosphoramidon can be attributed to the inhibition of NEP which may presumably cause an accumulation of ANF . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Angiotensin converting enzyme ( ACE ) and neutral endopeptidase ( NEP ) are implicated in the metabolism of several peptides involved in blood pressure and sodium homeostasis control , such as angiotensins , atrial natriuretic factor ( ANF ) , bradykinin and endothelin . ^^^ NEPI increased diuresis , natriuresis and urinary cyclic GMP ( cGMP ) , ANF and bradykinin in the three models . ^^^ CEI + NEPI increased diuresis and natriuresis in DOCA salt hypertensive rats and SHRs , and increased urinary cGMP , ANF and bradykinin and plasma renin levels . ^^^ Hence , NEPI increases diuresis , natriuresis and urinary cGMP , ANF and bradykinin in experimental hypertension , whereas CEI acts on blood pressure and increases in plasma renin in SHRs and renovascular hypertensive rats . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The role of NEP in ANF catabolism was demonstrated by incubating 125I ANF or unlabeled ANF for increasing periods of time with VSMC in the presence of thiorphan ( 1 100 microM ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral metalloendopeptidase ( NEP ) inhibitors delay atrial natriuretic factor ( ANF ) catabolism and potentiate biological responses to ANF . ^^^ The antihypertensive effect of SCH 42495 likely results from potentiation of endogenous ANF via NEP inhibition . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Currently work on therapeutic possibilities ( administration of exogenous ANF , combinations with NEP inhibitor / conversion enzyme inhibitor , ANF / diuretics ) have revealed certain problems ( short half life of ANF , transient effects , non specific activity of NEP ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Rates of metabolism of ANF ( pmol . min 1 . microgram protein 1 ) by renal cortical membranes from virgin ( n = 5 ) and gravid ( n = 5 ) rats were , respectively , 45 + / 0 . 6 and 45 + / 0 . 5 ; likewise , cortical membrane neutral endopeptidase activities in virgin and 20 day gravid rats ( n = 7 ) did not differ . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Atrial natriuretic factor ( ANF ) has natriuretic , renin suppressing and chronic hypotensive actions that may be utilized by inhibition of ANF degradation by neutral endopeptidase , E . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| It could be of therapeutic interest to associate prevention of angiotensin 2 formation , by inhibition of angiotensin 1 converting enzyme ( ACE ) , with potentiation of the ANF effects , by inhibition of neprilysin ( NEP ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Promising results were obtained in animal experiments and initial patient studies concerning haemodynamics and kidney function with inhibition of ANF metabolism by inhibitors of the neutral endopeptidase 24 . 11 ( NEP ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase ( NEP ) is the primary enzyme responsible for the degradation of ANF . ^^^ Neutral endopeptidase ( NEP ) is the primary enzyme responsible for the degradation of ANF . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| While ACE and ECE are respectively involved in the transformation of angiotensin 1 and Big ET into angiotensin 2 and ET 1 respectively , which possess vasoconstrictor and mitogenic properties , NEP is involved in the degradation of atrial natriuric factor ( ANF ) , which possesses vasorelaxant , diuretic / natriuretic and antihypertrophic properties . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| SCH 34826 , i . e . , ( S ) N ( N ( 2 , 2 [ ( 2 , 2 dimethyl 1 , 3 dioxolan 4 yl ) methoxy ] 2 oxo 1 ( phenyl methyl ) ethyl ) phenylalanyl ) beta alanine , is a potent and selective inhibitor of neutral endopeptidase 24 . 11 ( NEP ) , an enzyme that degrades the atrial natriuretic peptide ( ANP ) . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Atrial natriuretic peptide ( ANP ) is degraded by neutral endopeptidase ( NEP ) mainly in the proximal tubule of the kidneys . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Inhibition of intrarenal neutral endopeptidase 24 : 11 ( NEP ) increases the natriuretic response to infused atrial natriuretic peptide ( ANP ) . ^^^ In various models of canine heart failure , angiotensin and kinins have been shown to modulate ANP and ( or ) NEP activity . ^^^ In the present study , we examined possible modulators of NEP activity in normal dogs by infusing various agents into the left renal artery ( or by denervating the left kidney ) and comparing the response of this kidney with that of the contralateral one following the combined intravenous infusion of Squibb 28603 ( a potent NEP inhibitor ) and ANP ( 75 ng . kg 1 . min 1 ) . ^^^ Angiotensin inhibited sodium excretion following the NEP inhibitor alone and after the NEP inhibitor plus ANP . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The current study tested the hypothesis that chronic administration of the neutral endopeptidase ( NEP ) inhibitor Sch 34826 prevents NaCl sensitive hypertension in SHR S by increasing endogenous ANP . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Phosphoramidon , an inhibitor of neutral endopeptidase , did not enhance the SC 46542 response , indicating that C receptors predominate in ANP inactivation in these fish . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The results suggest that NEP inhibition may be a new therapeutic method for treating CHF possibly by potentiating the biological activities of endogenous ANP . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Since proximal tubule neutral endopeptidase 24 : 11 ( NEP ) destroys most of intrarenal luminal ANP and kinins , we attempted to convert TIVC NR into TIVC R by providing NEP inhibition with SQ 28603 at 30 mg / kg . ^^^ This potent and specific NEP inhibitor produced a natriuresis when administered alone to nine TIVC NR dogs ( delta UNaV = 67 + / 2 mu eq / min ) and permitted a natriuresis in the presence of ANP ( delta UNaV = 97 + / 18 mu eq / min ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Its inhibition by 1 , 10 phenanthroline , EDTA and bacitracin but not by thiorphan suggests the contribution of at least one neutral metalloendopeptidase , distinct from EC 3 . 4 . 24 . 11 , for which ANP showed high affinity . . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Despite high endogenous ANP levels in HF , NEP 1 further increases both ANP and its `` second messenger . ' ' Its natriuretic and hemodynamic effects are consistent with enhanced ANP activity in renal and vascular tissues , suggesting that NEP 1 may be useful for treating HF . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The depressor , natriuretic and cyclic GMP responses to several species of brain natriuretic peptide ( BNP ) were compared to atrial natriuretic peptide ( ANP ) 99 126 in conscious spontaneously hypertensive rats ( SHR ) and in conscious cynomolgus monkeys treated with vehicle or the selective neutral endopeptidase ( NEP 3 . 4 . 24 . 11 ) inhibitor N [ 2 ( mercaptomethyl ) 1 oxo 3 phenylpropyl ] beta alanine ( SQ 28 , 603 ) . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Candoxatril is a novel , orally active inhibitor of neutral endopeptidase EC 3 . 4 . 24 . 11 , the enzyme that degrades atrial natriuretic peptide ( ANP ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Regional haemodynamic responses to atrial natriuretic peptide ( ANP , 0 . 5 nmol kg 1 ) or proendothelin 1 [ 1 38 ] ( 1 . 0 nmol kg 1 ) were assessed in the same conscious Long Evans rats before and 20 min after administration of the novel neutral endopeptidase ( NEP ) inhibitor , SQ 28 , 603 ( 50 mg kg 1 , i . v . ) . ^^^ The results are consistent with SQ 28 , 603 not only inhibiting NEP that is involved in the degradation of ANP , but also suppressing activity of the enzyme involved in the conversion of proendothelin 1 [ 1 38 ] to endothelin 1 . . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Reduced urinary clearance of ANP may be associated with reduced filtered load and increased binding of ANP to the neutral endopeptidase 24 . 11 receptor binding sites in the proximal renal tubule . 4 . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The metalloproteinase , NEP 24 . 11 , is unlikely to be the cell surface peptidase because 125I ANP is degraded by CPA 47 cells at 4 degrees C in the presence of 5 mM EDTA . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| We have studied the acute effect of brain natriuretic peptide ( BNP ) and atrial natriuretic peptide ( ANP ) on pulmonary vascular tone in normoxia and acute hypoxia in the absence and presence of a specific inhibitor of neutral endopeptidase 24 . 11 ( NEI , UK 73 , 967 , candoxatrilat ; Pfizer ) in the isolated and blood perfused rat lung preparation . ^^^ Inhibition of neutral endopeptidase 24 . 11 augments the effects of ANP on HPV but does not influence the pulmonary vascular responses to BNP . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase ( NEP ; enkephalinase , EC 3 . 4 . 24 . 11 ) is a cell membrane associated zinc metalloprotease , which cleaves peptides like atrial natriuretic peptide ( ANP ) on the amino side of hydrophobic amino acids . ^^^ As the renal NEP can not account for the entire ANP metabolism , other locations were postulated . ^^^ Therefore , endothelial NEP could play an important role in the inactivation of ANP , bradykinin and endothelins by its localization facing the circulating vasoactive peptides . . ^^^ Neutral endopeptidase ( NEP ; enkephalinase , EC 3 . 4 . 24 . 11 ) is a cell membrane associated zinc metalloprotease , which cleaves peptides like atrial natriuretic peptide ( ANP ) on the amino side of hydrophobic amino acids . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase ( EC 3 . 4 . 24 . 11 ) is a wide spread enzyme that degrades atrial natriuretic peptide ( ANP ) . ^^^ Neutral endopeptidase ( EC 3 . 4 . 24 . 11 ) is a wide spread enzyme that degrades atrial natriuretic peptide ( ANP ) . ^^^ Inhibition of neutral endopeptidase therefore amplifies the actions of endogenous ANP on blood pressure and fluid partition . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Inhibition of ANP degradation by NEP in the kidney by the new NEP or atriopeptidase inhibitors may explain their natriuretic and diuretic effect in the absence of changes in plasma ANP levels . ^^^ Atrial natriuretic peptide ( ANP ) is rapidly degraded by neutral metalloendopeptidase ( EC 3 . 4 . 24 . 11 , NEP ) , with the kidney being a major site of ANP clearance . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| SCH 34826 elevates plasma ANP by inhibition of the enzyme neutral endopeptidase EC 3 . 4 . 24 . 11 . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| To explore the roles of endogenous atrial natriuretic peptide ( ANP ) in the volume regulation , we examined effects of antiserum for ANP or a neutral endopeptidase inhibitor , thiorphan , in rats with monocrotaline ( MCT ) induced pulmonary hypertension . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Outside the CNS , the progressive appearance of NEP in the kidney , the lungs and the salivary glands suggests its concomitant involvement in adult physiological functions , including fluid balance control , possibly by cleaving the atrial natriuretic peptide ( ANP ) and other peptides . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase ( NEP ; enkephalinase , EC 3 . 4 . 24 . 11 ) is a cell membrane associated zinc metalloprotease , which cleaves peptides like atrial natriuretic peptide ( ANP ) on the amino side of hydrophobic amino acids . ^^^ As the renal NEP can not account for the entire ANP metabolism , other locations were postulated . ^^^ Therefore , endothelial NEP may play an important role in the inactivation of ANP , bradykinin , and endothelins by its localization facing the circulating vasoactive peptides . . ^^^ Neutral endopeptidase ( NEP ; enkephalinase , EC 3 . 4 . 24 . 11 ) is a cell membrane associated zinc metalloprotease , which cleaves peptides like atrial natriuretic peptide ( ANP ) on the amino side of hydrophobic amino acids . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Beside renal clearance , an extra renal metabolism by the enzyme neutral endopeptidase 24 . 11 ( NEP 24 . 11 ) has been proposed , since specific NEP 24 . 11 inhibitors increase endogenous plasma ANP . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The effects of a neutral endopeptidase ( NEP ) inhibitor , SCH 39 . 370 , and a clearance receptor ligand , C atrial natriuretic factor ( 4 23 ) [ C ANF ( 4 23 ) ] on the plasma concentration of atrial natriuretic peptide ( ANP ) and hemodynamics under basal conditions and during increased circulating ANP levels produced by acute volume loading in conscious rats were studied . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| To explore the mechanisms for the natriuretic effects of a neutral endopeptidase inhibitor , candoxatril , the concentration of atrial natriuretic peptide ( ANP ) and its molecular forms in the urine of Dahl salt sensitive ( S ) rats were examined . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| To determine the relative contribution of ANP clearance ( C ) receptors and neutral endopeptidase 24 . 11 ( NEP ; EC 3 . 4 . 24 . 11 ) in regulation of plasma ANP concentration ( [ ANP ] ) during maturation , 18 to 60 day old male Sprague Dawley rats were anesthetized and infused with rat ANP ( 35 ng . kg 1 . min 1 ) . ^^^ Infusion of the NEP inhibitor phosphoramidon increased [ ANP ] and urine guanosine 3 ' , 5 ' cyclic monophosphate ( cGMP ) excretion in both weanling and adult rats . ^^^ These results indicate that both C receptors and NEP modulate plasma [ ANP ] in the physiological range and that each pathway compensates when the other is inhibited . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| In conclusion , the profile of depressor and renal activities produced by SQ 29 , 072 was consistent with potentiation of endogenous ANP by inhibition of NEP in conscious SHR and DOCA / salt hypertensive rats . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| SQ 28 , 603 is a potent and selective inhibitor of neutral endopeptidase 3 . 4 . 24 . 11 ( NEP ) , an enzyme that degrades atrial natriuretic peptide ( ANP ) . ^^^ In conclusion , inhibition of NEP activity by SQ 28 , 603 significantly decreased MAP and increased plasma ANP concentrations and urinary excretion of cyclic GMP in conscious DOCA / salt hypertensive rats . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The observation that NEP inhibition has more pronounced effects in animals with high ambient ANP level than in those with normal ANP is consistent with previous studies in a variety of animal models and supports the concept that NEP inhibition potentiates endogenous ANP . . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| We conclude that acute atriopeptidase inhibition by UK 79300 effectively increases endogenous ANP levels up to 2 . 5 fold . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase 24 . 11 , a metallopeptidase , is known to inactivate atrial natriuretic peptide ( ANP ) , a substance with diuretic , natriuretic , and vasodilatory effects . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Atrial natriuretic peptide ( ANP ) is degraded by neutral metalloendopeptidase ( NEP ) ( EC 3 . 4 . 24 . 11 ) and the kidney is a major site of ANP clearance . 2 . ^^^ The present result suggests that degradation of ANP by NEP occurs mainly in the proximal tubules of the juxtamedullary nephrons , rather than cortical nephrons , and that the convoluted tubule in the OC is not a major site of location of NEP . 7 . ^^^ The relationship between NEP activities in the kidney in vitro and plasma clearance of ANP in vivo remains to be clarified . . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Inhibition of the metabolism of endogenous atrial natriuretic peptide ( ANP ) , by continuous infusion of a specific inhibitor of neutral endopeptidase ( membrane metalloendopeptidase E . ^^^ Inhibition of neutral endopeptidase 24 . 11 with low dose and high dose UK 73 , 967 ( NEI ) increased endogenous plasma ANP by greater than 155 % during the development of pulmonary hypertension . ^^^ Retarding the metabolism of endogenous ANP through inhibition of neutral endopeptidase 24 . 11 represents a potential approach toward therapy . g . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| This also the case for aminopeptidase N ( APN ) and neutral endopeptidase 24 . 11 ( NEP , CALLA ) which together inactivate the endogenous opioid peptides , enkephalins , whereas only NEP is involved in the metabolism of the atrial natriuretic factor ( ANP ) at the kidney and vascular levels . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The neutral endopeptidase 24 . 11 ( NEP ) also called ' enkephalinase ' thanks to its inactivation of enkephalins in the brain , was also recently shown to be involved in the degradation of the circulating atrial natriuretic peptide ( ANP ) . ^^^ Except for the brain , the physiological function of NEP in various tissues remains largely unknown , but this ectoenzyme is likely involved in inactivation of regulatory peptides such as : ANP ( partially in the kidney ) , SP in the lung and possibly somatostatin and ANP in bone , ANP in adipose tissue , enkephalin in testes , immune peptidic factors in bone marrow . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase 24 . 11 , an enzyme known to degrade ANP , has been implicated in the metabolic clearance of this hormone . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| We conclude that the NEP inhibitory compound SCH 39370 is capable of increasing plasma ANP concentration and urinary excretion of cGMP in rats with chronic CHF . ^^^ NEP inhibitors offer a novel approach to study the significance of ANP elevation in chronic CHF . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Further studies are needed to assess the pathophysiological significance of ANP in diabetes mellitus and cirrhosis , and to define the indications of the treatment by enkephalinase inhibitors which increase endogenous ANP levels by lowering the catabolism of this hormone . . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| In previous studies , neutral endopeptidase ( NEP ) hydrolyzed the Cys 105 Phe106 bond of atrial natriuretic peptides ( ANP ) in vitro . ^^^ In conscious spontaneously hypertensive rats ( SHR ) in the present study , 100 mumol / kg , intravenously ( i . v . ) of the NEP inhibitor , SQ 29 , 072 ( 7 [ [ 2 ( mercaptomethyl ) 1 oxo 3 phenyl propyl ] amino ] heptanoic acid ) , significantly increased the area over the curve ( AOC ) of the depressor response to 3 nmol / kg of ANP 103 126 from 165 + / 36 to 792 + / 350 , 1 , 515 + / 374 , and 828 + / 164 mm Hg . min at 15 , 30 , and 60 min after inhibitor treatment . ^^^ In conclusion , NEP may inactivate ANP in vivo by cleavage of susceptible bonds within the ANP ring . . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Endoprotease EC 3 . 4 . 24 . 11 ( NEP 24 . 11 ) , present within the kidney in high concentration , has been shown in vitro to degrade ANP . ^^^ Phosphoramidon and thiorphan , two potent NEP 24 . 11 inhibitors , have been shown to prevent the enzymatic degradation of ANP . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase ( NEP , EC 3 . 4 . 24 . 11 ) , purified from renal brush border , cleaves the Cys 7 Phe8 amide bond of rat atrial natriuretic peptide ( ANP ) , to generate the inactive metabolite ( ANP cleaved at the Cys 7 Phe8 bond ; 10 ANP ) . ^^^ To determine if NEP contributes to the inactivation of circulating ANP , we investigated the degradation of rat ANP ( rANP , 1 28 ) in the vasculature . ^^^ Formation of 10 ANP from exogenous ANP was studied in a mesenteric arterial preparation by perfusion in a single pass system in the presence and absence of the NEP inhibitors , thiorphan or phosphoramidon . ^^^ These studies indicate that ANP is degraded in the vasculature by NEP or an `` NEP like ' ' enzyme ( s ) . . ^^^ Neutral endopeptidase ( NEP , EC 3 . 4 . 24 . 11 ) , purified from renal brush border , cleaves the Cys 7 Phe8 amide bond of rat atrial natriuretic peptide ( ANP ) , to generate the inactive metabolite ( ANP cleaved at the Cys 7 Phe8 bond ; 10 ANP ) . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| To investigate the in vivo effects of inhibition of endopeptidase 24 . 11 , an enkephalinase enzyme shown to be involved in atrial natriuretic peptide ( ANP ) breakdown in vitro , we infused phosphoramidon , a specific inhibitor of endopeptidase 24 . 11 , into rats with reduced renal mass ( and chronic extracellular volume expansion ) and into normal rats . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Thirty nmole / kg of ANP 103 123 , a possible product of NEP cleavage of ANP 103 126 , produced a lesser AOC ( 442 + / 152 mm Hg 10 min ) than did either of the longer peptides . ^^^ In conclusion , three ring opened products of NEP cleavage of ANP 99 126 , 103 126 and 103 123 were inactive in conscious SHR . . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Thus , the effects of NEP inhibition appear to be potentiated by the reduced receptor mediated metabolism of ANP . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Interaction of a neutral endopeptidase inhibitor with an ANP C receptor ligand in anesthetized dogs . ^^^ The aim was to investigate the in vivo effects of both blockade of atrial natriuretic peptide clearance receptor and inhibition of neutral endopeptidase 24 . 11 , an enzyme shown to be involved in ANP breakdown . ^^^ Therefore , we infused a specific neutral endopeptidase inhibitor ( ( S ) thiorphan ) and an ANP C receptor ligand ( AP 811 ) alone or in combination into anaesthetized beagle dogs . ^^^ We conclude from these investigations , that blocking both degrading pathways of ANP with the ANP C receptor ligand AP 811 and the neutral endopeptidase inhibitor ( S ) thiorphan is more effective than inhibition of either system alone . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| These results clearly demonstrate that NEP does not contribute to the in vivo clearance of ET and support the hypothesis that NEP plays an important role in clearance of ANP from the circulation . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| It is also well known that NEP metabolizes atrial natriuretic peptide ( ANP ) . ^^^ The present study evaluated the effects of NEP inhibitor on renal action by kinins , ANP and nitric oxide in Sprague Dawley normotensive rats and DOCA salt hypertensive rats . ^^^ In normotensive rats , we demonstrated that 1 ) inhibition of NEP potentiates the contribution of kinins to the renal water sodium metabolism and overcomes the contribution of ANP to that metabolism , 2 ) nitric oxide participates in the action of kinins , and 3 ) changes in urinary cGMP excretion do not reflect the changes in plasma ANP , but the changes in nitric oxide , under these conditions . ^^^ On the other hand , it was also suggested that augmented ANP may contribute mainly to renal water sodium handling by NEP inhibitor in DOCA salt rats . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase ( NEP ) is a widely distributed enzyme that participates in ANP catabolism , whereas cGMP phosphodiesterase ( PDE ) degrades the intracellular second messenger of ANP . ^^^ Therefore , we examined the consequences of inhibition of NEP and PDE on the ANP dependent activity described above using the NEP inhibitor SQ 28 , 603 and the cGMP PDE inhibitor zaprinast ( M & B 22 , 948 ) . ^^^ Modulation of ANP dependent effects of endothelin by inhibitors of neutral endopeptidase and cGMP phosphodiesterase . ^^^ Neutral endopeptidase ( NEP ) is a widely distributed enzyme that participates in ANP catabolism , whereas cGMP phosphodiesterase ( PDE ) degrades the intracellular second messenger of ANP . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The reduced ability of inhaled compared with intravenous atrial natriuretic peptide ( ANP ) to modify bronchial reactivity and tone may be due to degradation of the peptide by neutral endopeptidase ( NEP ) within the airways . ^^^ To test this hypothesis , we have examined the effect of thiorphan , an NEP inhibitor , on the protection afforded by inhaled ANP against histamine induced bronchoconstriction in 10 mildly asthmatic patients . ^^^ Our results suggest that airway NEP is important in modulating the effect of inhaled ANP . ^^^ It may be possible to exploit the guanylyl cyclase pathway , by which ANP acts , in the treatment of asthma by the administration of ANP analogues stable to neutral endopeptidase . . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Inhibitors of neutral endopeptidase ( NEP ) EC 3 . 4 . 24 . 11 were developed to regulate endogenous levels of the natriuretic and vasodilatory hormone atrial natriuretic peptide ( ANP ) . ^^^ The selective NEP inhibitor SQ 28603 enhanced the increases in plasma ANP and urinary excretion of ANP , cyclic GMP and sodium stimulated by infusion of human ANP in conscious monkeys . ^^^ Selective NEP inhibitors lowered blood pressure in conscious DOCA / salt hypertensive rats and SHR with antihypertensive activity similar to that of exogenous ANP . ^^^ The novel dual metalloprotease inhibitor BMS 182657 potentiated the renal responses to exogenous ANP and suppressed the pressor response to angiotensin 1 in conscious monkeys , indicating in vivo inhibition of both NEP and ACE . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Previous studies , using neutral endopeptidase EC 3 . 4 . 24 . 11 ( NEP ) derived from crude membrane preparations , were inconclusive , but suggested that urodilatin was more resistant than ANP to degradation by this enzyme . ^^^ In the present study , we compared the degradation rates of [ 125I ] urodilatin and [ 125I ] ANP by pure recombinant NEP ( rNEP ) . 2 . ^^^ These results support the relative resistance of urodilatin to NEP , and indicate that urodilatin may be of use as a therapeutic agent , in conditions in which ANP is ineffective . . ^^^ Hydrolysis of iodine labelled urodilatin and ANP by recombinant neutral endopeptidase EC . 3 . 4 . 24 . 11 . 1 . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase ( NEP ) is involved in the metabolism of atrial natriuretic peptide ( ANP ) , whereas angiotensin converting enzyme ( ACE ) is involved in the metabolism of angiotensin 1 ; both enzymes participate in bradykinin metabolism . ^^^ Neutral endopeptidase ( NEP ) is involved in the metabolism of atrial natriuretic peptide ( ANP ) , whereas angiotensin converting enzyme ( ACE ) is involved in the metabolism of angiotensin 1 ; both enzymes participate in bradykinin metabolism . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| To further elucidate the natriuretic mechanisms of neutral endopeptidase 24 . 11 ( NEP ) inhibition , we employed a new specific NEP inhibitor , UK 73967 ( UK ) , with or without a specific kinin receptor antagonist , Hoe 140 ( Hoe ) , in Sprague Dawley rats , and evaluated the renal NEP , kinins and plasma ANP simultaneously . ^^^ From these results , we conclude that inhibition of NEP may exaggerate the contribution of renal kinins to the renal water sodium metabolism and overcome the contribution of ANP on that metabolism at least in normotensive rats . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Therefore , the non human primate model was appropriate for investigating the effects of sodium loads on the urinary ANP and cGMP responses to exogenous ANP in the presence and absence of NEP inhibitors . 3 . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| One route of ANP metabolism in vivo is by the action of the enzyme neutral endopeptidase ( NEP ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Metabolism by NEP is one of the main mechanisms for the clearance of atrial natriuretic peptide ( ANP ) , a hormone that causes bronchodilation and reduces nonspecific bronchial reactivity in man . ^^^ Candoxatril , an oral NEP inhibitor has been shown to elevate circulating ANP levels . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| CGS 26303 is a potent and structurally unique non peptidic inhibitor of neutral endopeptidase ( NEP ) capable of protecting atrial natriuretic peptide ( ANP ) from enzymatic degradation . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| To study the possible physiological role of atrial natriuretic peptide ( ANP ) in the regulation of intraocular pressure ( IOP ) the effects of an increase of endogenous ANP within the physiological range induced by the neutral endopeptidase 24 . 11 ( NEP ) inhibitor candoxatril were examined . ^^^ The reduction in IOP with chronic NEP inhibition was positively correlated with the increase in ANP levels but not with changes in blood pressure . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| METHODS : We examined effects of a neutral endopeptidase inhibitor , candoxatril , on plasma and urinary brain natriuretic peptide ( BNP ) levels , the influence of a specific atrial natriuretic peptide ( ANP ) receptor antagonist , HS 142 1 , on the response to candoxatril , and the renal neutral endopeptidase activity in DOCA salt rats . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Activity and localization of neutral metalloendopeptidase ( EC 3 . 4 . 24 . 11 ) ( NEP ) , the degradative enzyme for atrial natriuretic peptide ( ANP ) , in rat kidney ] . ^^^ Atrial natriuretic peptide ( ANP ) is degraded by neutral metalloendopeptidase ( EC 3 . 4 . 24 . 11 ) ( NEP ) , and the kidney is the major site of ANP clearance . ^^^ The present result suggests that degradation of ANP by NEP occurs mainly in the deep proximal tubules , and that the proximal convoluted tubule in the outer cortex is not a major site of location of NEP . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Endopeptidase 24 . 11 ( E 24 . 11 , EC 3 . 4 . 24 . 11 ) is widely believed to play a physiological role in metabolizing atrial natriuretic peptide ( ANP ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase ( NEP ) inhibitors have been shown to strengthen the effects of endogenous atrial natriuretic peptide ( ANP ) . ^^^ Neutral endopeptidase ( NEP ) inhibitors have been shown to strengthen the effects of endogenous atrial natriuretic peptide ( ANP ) . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| In the treatment of cardiovascular diseases , it could be of therapeutic interest to associate the hypotensive effects resulting from the inhibition of angiotensin 2 formation , ensured by endothelial angiotensin converting enzyme ( ACE ) , with the diuretic and natriuretic responses due to the protection of the endogenous atrial natriuretic peptide ( ANP ) from inactivation by epithelial neutral endopeptidase ( NEP ) . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Investigation of this hypothesis requires an orally active compound able to simultaneously inhibit angiotensin converting enzyme ( ACE ) and neutral endopeptidase ( NEP ) , which is involved in renal ANP metabolism . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| ANP is metabolized in rat lung membrane preparations by the enzyme neutral endopeptidase 24 . 11 ( EC 3 . 4 . 24 . 11 ) , but the hydrolysis of ANP in human lung has not been characterized . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Ex vivo experiments showed that , at variance with bestatin , the hypoalgesic action of Z 4212 or Z 1796 appeared to implicate central aminopeptidases but not NEP , so partially sparing the metabolism of other NEP substrates that might produce additional alterations ( substance P and ANP ) . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| In addition , neutral endopeptidase contributes to removal of circulating ANP in maturing as well as adult rats . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Seven patients with chronic heart failure were treated in single blind crossover fashion with placebo and 10 mg , 50 mg , and 200 mg doses of the neutral endopeptidase inhibitor candoxatril to determine the effects of candoxatril on the elimination kinetics of exogenously infused atrial natriuretic peptide ( ANP ) . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase ( NEP ) inhibition is thought to blunt hypoxic pulmonary hypertension by reducing atrial natriuretic peptide ( ANP ) metabolism , but this hypothesis has not been confirmed . ^^^ We measured NEP activity , guanosine 3 ' , 5 ' cyclic monophosphate ( cGMP ) production , plasma ANP levels , and cardiac ANP synthesis in rats given an orally active NEP inhibitor ( SCH 34826 ) during 3 wk of hypoxia . ^^^ Under normoxic conditions , SCH 34826 had no effect on plasma ANP levels but reduced pulmonary and renal NEP activity by 50 % and increased urinary cGMP levels ( 60 + / 6 vs . 22 + / 4 pg / mg creatinine ; P < 0 . 05 ) . ^^^ We conclude that NEP inhibition blunts pulmonary hypertension without increasing plasma ANP levels . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^ Neutral endopeptidase ( NEP ) inhibition is thought to blunt hypoxic pulmonary hypertension by reducing atrial natriuretic peptide ( ANP ) metabolism , but this hypothesis has not been confirmed . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Inhibition of ANP / BNP metabolism by neutral endopeptidase has been shown to attenuate development of hypoxic pulmonary hypertension but this property has not been tested in humans . 4 . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| To further investigate the mechanisms of renal effects of neutral endopeptidase 24 . 11 ( NEP ) inhibition , we employed a specific NEP inhibitor , UK 73967 ( UK ) , with or without a specific kinin receptor antagonist , Hoe 140 ( Hoe ) , or nitric oxide ( NO ) synthase inhibitor , N monomethyl L arginine ( L NMMA ) , in Sprague Dawley rats , and evaluated the urinary NEP , kinins , cGMP and plasma atrial natriuretic peptide ( ANP ) . ^^^ In conclusion , augmented kinins may play an important role in the renal water sodium metabolism by NEP inhibition , and NO may contribute to the kinins ' action on this mechanism , while ANP may not contribute to it , at least in normotensive rats . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| In Sprague Dawley rats : 1 ) injected UK significantly decreased NEP , and increased kinins , urine volume ( UV ) and urinary sodium excretion ( UNaV ) , while none of the variables changed with vehicle treatment ; 2 ) no difference was found in plasma ANP between the vehicle and UK groups ; and 3 ) Hoe canceled the increases of UV and UNaV caused by UK . ^^^ In DOCA salt rats : 1 ) infused UK significantly decreased NEP , and increased UV and UNaV , while UV and UNaV were slightly decreased , and NEP did not change with vehicle treatment ; 2 ) plasma ANP was significantly higher in UK group than in the vehicle group ; and 3 ) Hoe could not abolish the increase of UV and UNaV induced by UK . ^^^ These data indicate that the contributions of renal kinins and plasma ANP to the diuretic and natriuretic mechanisms of NEP inhibition may differ between Sprague Dawley normotensive rats and DOCA salt hypertensive rats . . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| It exerts antihypertensive effects by potentiating atrial natriuretic peptide ( ANP ) activity through inhibition of its hydrolysis by NEP . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Both in vitro and in vivo studies have found that the protective effect of ANP against bronchoconstriction is enhanced by inhibition of the enzyme neutral endopeptidase ( NEP ) . ^^^ It was hypothesised that pretreatment with thiorphan , an NEP inhibitor , might enhance the bronchodilator response to inhaled ANP . ^^^ The degree and duration of the bronchodilator response produced by ANP , or the combination of the NEP inhibitor and ANP , were less than that produced by salbutamol . ^^^ CONCLUSIONS : These results confirm that , at least in part , the bronchodilator response to inhaled ANP is modulated by NEP . ^^^ Analogues of ANP which are stable to NEP may have greater bronchodilator activity than ANP in the treatment of asthma . . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Therefore , future treatment of chronic heart failure or asymptomatic left ventricular dysfunction might include beta adrenergic blockers , neutral endopeptidase inhibitors , ANP , BNP , angiotensin 2 receptor antagonists , and modulators of sympathetic activity . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| PAMP is rapidly cleaved by human neutral endopeptidase ( NEP ) , a protease which plays a key role in the degradation of human atrial natriuretic peptide ( ANP ) . ^^^ The present data suggest that NEP may be involved in the circulation control by degrading PAMP as well as ANP . . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| This study was performed to determine effects of atrial and brain natriuretic peptides ( ANP , BNP ) on neutrophils induced endothelial injury which is known to play a role in the pathophysiology of ischemia / reperfusion myocardial injury and to examine whether the effects of ANP and BNP on neutrophils are modulated by neutral endopeptidase 24 . 11 ( NEP ) in neutrophils themselves . ^^^ Coincubation with UK 73967 or phosphoramidon , inhibitors of NEP , potentiated all of the effects of ANP and BNP on the neutrophil functions , and the NEP inhibitors protected degradation of ANP and BNP by the neutrophils . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| BNP has a lower affinity than ANP for C ( clearance ) receptors , and is less susceptible to degradation by neutral endopeptidase 24 . 11 , resulting in a longer half life . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| After 4 weeks of observation the ANP and BNP plasma levels , renin activity ( PRA ) , angiotensin 1 , and neutral endopeptidase activity were significantly higher in AVF rats than in sham operated rats . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Inhibition of neutral endopeptidase protects endogenous ANP , and inhibition of angiotensin converting enzyme blocks angiotensin 2 production , whereas inhibition of both peptidases is required to protect endogenous bradykinin ( BK ) . ^^^ Inhibition of both angiotensin converting enzyme and neutral endopeptidase by potentiating endogenous ANP and BK and blocking angiotensin 2 production could be an interesting therapeutic approach in heart failure . . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| ANP is partly metabolized by NEP . ^^^ That an inhibitor of NEP increased the potency of ANP in isolated pulmonary vessels , and in isolated perfused whole lungs , suggested that SCH 42354 may be having a local action within the pulmonary vasculature . . ^^^ Neutral endopeptidase inhibition increases the potency of ANP in isolated rat pulmonary resistance vessels and isolated blood perfused lungs . ^^^ We have investigated the effects of the neutral endopeptidase inhibitor , SCH 42354 , on the vasoreactivity of atrial natriuretic peptide ( ANP ) in rat isolated pulmonary resistance vessels ( PRV ) and isolated perfused lungs ( IPL ) . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase ( NEP ) EC 3 . 4 . 24 . 11 is a zinc metallopeptidase which is partly responsible for the degradation of atrial natriuretic peptide ( ANP ) in vivo . 2 . ^^^ Thus , attenuating the metabolism of this peptide using NEP inhibitors , should potentially enhance the effects of ANP , either by maintaining plasma levels or at a local , tissue level . . ^^^ Neutral endopeptidase ( NEP ) EC 3 . 4 . 24 . 11 is a zinc metallopeptidase which is partly responsible for the degradation of atrial natriuretic peptide ( ANP ) in vivo . 2 . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The NEP activity in plasma was significantly inhibited and the plasma levels of atrial ( ANP ) and brain ( BNP ) natriuretic peptides and their second messenger , cyclic GMP , were distinctly raised after oral administration . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The present study examined the effect of exogenous atrial natriuretric peptide ( ANP ) , alone or in presence of inhibitors of the two major mechanisms for clearing ANP , metabolism by neutral endopeptidase 24 . 11 ( NEP ) and internalization by C ANP receptors , on arteriolar responses using intravital microscopy on the rat cremaster muscle after intravenous or topical administration of the peptide . 2 . ^^^ NEP inhibitors , thiorphan ( 30 mg kg 1 , i . v . ) , kelatorphan ( 10 mg kg 1 , i . v . ) and retrothiorphan ( 25 mg kg 1 , i . v . ) alone , did not significantly affect vascular tone but caused significant potentiation of the arteriolar responses to topically applied ANP . 3 . ^^^ These results indicate that low doses of topically applied ANP dilate rat cremaster arterioles and that the vasodilator responses can be potentiated by NEP inhibition . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Because kinins are also metabolized by neutral endopeptidase ( NEP ) 24 . 11 in vivo , we hypothesized that ( a ) inhibition of NEP 24 . 11 would afford cardioprotection similar to that of ACEi and potentiate the effect of ACEi ; and ( b ) these effects are mediated by kinins or atrial natriuretic peptide ( ANP ) or both . ^^^ To test whether the effect of NEPi could be suppressed by blocking kinins or ANP , the kinin receptor antagonist icatibant or ANP antagonist HS 142 1 was administered before LAD occlusion . ^^^ The effect of NEPi was slightly diminished by the ANP antagonist HS 142 1 ( infarct size / risk area , 35 + / 3 % ; NS vs . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| AIMS : Candoxatril is a specific neutral endopeptidase ( NEP ) 24 . 11 inhibitor , and previous work has documented the effect of NEP inhibition on atrial and brain natriuretic peptides ( ANP , BNP ) . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| We conclude that ( 1 ) circulating CNP achieved by exogenous CNP infusion is regulated by NEP in vivo , ( 2 ) regional MCRs are heterogeneous with NEP inhibition , ( 3 ) NEP inhibition does not potentiate acute cardiovascular actions of CNP , and ( 4 ) a mild natriuretic and diuretic effect observed with CNP and NEP inhibition may be ANP dependent . . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Intravenous SCH 39370 induced a dose related inhibition of NEP activity during 4 days treatment , in association with a transient increase in plasma atrial natriuretic peptide ( ANP ) and , at the higher dose , an increased mean level of plasma cyclic guanosine monophosphate . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| To evaluate the interaction between renal nerves , the atrial natriuretic peptide ( ANP ) , and the renin angiotensin system ( RAS ) , electrical stimulation of renal nerves was performed in spontaneously hypertensive rats ( SHR ) and in their normotensive controls , Wistar Kyoto rats ( WKY ) , before and after pharmacologic treatment with ( a ) a neutral endopeptidase inhibitor ( NEP 1 ) to enhance the intrarenal ANP activity ; ( b ) an ACE inhibitor ( ACE 1 ) to block RAS ; ( c ) both NEP 1 and ACE 1 ; and ( d ) the vehicle of the drugs . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The influence of neutral endopeptidase ( NEP ) inhibition with ( S ) thiorphan on the hormonal , renal , and blood pressure lowering effects of an infusion of atrial ( ANP ) , brain ( BNP ) , and C type natriuretic peptide ( CNP ) was evaluated in hypertensive transgenic rats ( TGR ) harboring an additional mouse renin gene ( TGR ( m ( Ren 2 ) 27 ) ) . ^^^ Co administration of ANP , BNP , or CNP with the NEP inhibitor ( S ) thiorphan potentiated the plasma ANP , BNP , and cGMP . ^^^ These results indicate that inhibition of neutral endopeptidase by ( S ) thiorphan potentiates the hemodynamic and renal effects of natriuretic peptides ANP and BNP , and to some extent those of CNP , in hypertensive TGR and normotensive SDR . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| OBJECTIVES : Inhibition of neutral endopeptidase 24 . 11 ( NEP ) prevents degradation of plasma atrial natriuretic peptide ( ANP ) , a substance with vasodilatory and natriuretic properties . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase inhibition prevented atrial natriuretic peptide ( ANP ) degradation in endothelial and smooth muscle cells . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase inhibition ( NEPI ) provides a potential avenue to modulate the actions of atrial natriuretic peptide ( ANP ) . ^^^ ANP plasma levels and cGMP excretion were significantly increased with acute NEPI by SQ 28 . 603 , whereas chronic inhibition with SCH 34826 did not lead to any changes . ^^^ After acute volume expansion , ANP increased five fold with acute NEPI , whereas it only increased about 70 % in chronically inhibited rats . ^^^ Together with an increased cGMP / ANP ratio , these data suggest that chronic activation of the renal ANP system after long term NEPI facilitated the excretion of an acute volume load . ^^^ Neutral endopeptidase inhibition ( NEPI ) provides a potential avenue to modulate the actions of atrial natriuretic peptide ( ANP ) . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The substrates of CD10 / NEP in the kidneys are ( see the list of abbreviations ) ANP , adrenomedullin and PAMP ; in the brain , the substrates are enkephalins and oxytocin ; in the lung , bombesin , BLP , GRP , neuromedin C , substance P and neurokinin A ; in the cardiovascular system , angiotenisin 2 , bradykinin and CGRP ; in the gut , VIP ; on the neutrophil membrane , fMLP etc . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Activity of the major ANP degrading enzyme , neutral endopeptidase ( NEP , EC 3 . 4 . 24 . 11 ) , was 15 times higher in the pericardial fluid than in plasma . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Dual angiotensin converting enzyme ( ACE ) / neutral endopeptidase ( NEP ) inhibitors , by decreasing angiotensin 2 production and by preventing the degradation of atrial natriuretic peptide ( ANP ) , may be useful for the treatment of hypertension and congestive heart failure . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Systemic clearance of atrial natriuretic peptide ( ANP ) is in part due to neutral endopeptidase ( NEP ) proteolysis and natriuretic peptide receptor C ( NPR C ) mediated endocytosis . ^^^ Analogs of ANP selective for NPR A and / or resistant to NEP may have increased activity in those tissues where NPR C and NEP are coexpressed with NPR A . ^^^ As an alternative approach we tested the binding and potency of receptor selective and NEP resistant ANP analogs in rhesus monkey tissues . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| These results suggest that oral administration of the NEP inhibitor SCH 34826 inhibits renal neutral endopeptidase , increases urinary ANP and modulates natriuresis without alteration of systemic blood pressure , plasma ANP and renin level , glomerular filtration or protein excretion . . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Endogenous plasma ANP was augmented more than BNP by NEP inhibition . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| To investigate whether neutral endopeptidase inhibition ( NEP 1 ) increases endogenous atrial natriuretic peptide ( ANP ) and enhances natriuresis and diuresis after heart transplantation , ecadotril was given orally to 8 control subjects and 8 matched Htx , and levels of volume regulating hormones and renal water , electrolyte , and cyclic guanosine monophosphate ( cGMP ) excretions were monitored for 210 minutes . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| By RT PCR and DNA sequencing , we demonstrated that the CE and NPE cells express mRNA for ( 1 ) ANP ; ( 2 ) BNP ; ( 3 ) NPR A , NPR B , and NPR C receptors ; and ( 4 ) the neutral endopeptidase 24 . 11 . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The cGMP formation stimulated by ANP in LLC PK 1 cells was significantly decreased by pre treatment of the peptide with rat renal brush border membranes , and the inactivation of ANP was inhibited by neutral endopeptidase inhibitors , phosphoramidon and S thiorphan . ^^^ These results suggest that enzymatic degradation of natriuretic peptides is highly dependent on peptide structure , and that the affinity of BNP to neutral endopeptidase is less than that of ANP . . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Simultaneous inhibition of NEP and ACE increases natriuretic and vasodilatory peptides ( including atrial natriuretic peptide [ ANP ] , brain natriuretic peptide [ BNP ] of myocardial cell origin , and C type natriuretic peptide [ CNP ] of endothelial cell origin ) and increases the half life of other vasodilator peptides including bradykinin and adrenomedullin . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| BACKGROUND : Neutral endopeptidase 24 . 11 ( NEP ) is a metalloprotease that is localized in the greatest abundance in the kidney and degrades natriuretic peptides , such as atrial natriuretic peptide ( ANP ) . ^^^ These studies underscore the potential therapeutic role for NEP inhibition to enhance renal function in mild CHF , an important phase of CHF that is marked by selective activation of endogenous ANP in the absence of an activated RAAS . . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| BACKGROUND : MDL 100 , 240 ( pyrido [ 2 , 1 a ] [ 2 ] benzazepine 4 carboxylic acid , 7 [ [ 2 ( acetylthio ) 1 oxo 3 phenylpropyl ] amino ] 1 , 2 , 3 , 4 , 6 , 7 , 8 , 12b octahydro 6 oxo , [ 4S [ 4alpha , 7alpha ( R ( * ) ) , 12bbeta ] ] ) is a molecule possessing an inhibiting ability on both angiotensin converting enzyme ( ACE ) and neutral endopeptidase , the enzyme responsible for atrial natriuretic peptide ( ANP ) degradation . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Thiorphan , a neutral endoprotease ( NEP ) enzyme inhibitor , has been shown to enhance the effects of atrial natriuretic peptide ( ANP ) in vivo . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| It is also by a urinary pathway via the macula densa that ANP , and its potentiation by NEP inhibition , decreases renin secretion . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| In this study , the most appropriate BG subtraction method was evaluated as compared with plasma atrial natriuretic peptide ( ANP ) , brain natriuretic peptide ( BNP ) , norepinephrine ( NEP ) and left ventricular ejection fraction ( LVEF ) . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| All treatments reduced plasma aldosterone levels ( P < 0 . 01 ) , and NEP inhibition with SCH 42495 and S 21402 increased plasma atrial natriuretic peptide ( ANP ; P < 0 . 05 ) . ^^^ The dual NEP / ACE inhibitor S 21402 offered no advantage over the selective ACE inhibitor in terms of blood pressure reduction , or attenuation of cardiac hypertrophy and fibrosis , but did increase plasma ANP and blunted the reactive rise in renin with ACE inhibition . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| In contrast , atrial natriuretic peptide ( ANP ) is a potent vasorelaxant and diuretic , and it is mainly degraded by neutral endopeptidase 24 . 11 ( NEP ) . ^^^ Therefore , compounds that can suppress the production of ET 1 by inhibiting ECE while simultaneously potentiating the levels of ANP by inhibiting NEP may be novel agents for the treatment of cardiovascular and renal dysfunction . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Insofar as neutral endopeptidase inhibition has afforded evidence for a tubular luminal action of atrial natriuretic peptide ( ANP ) , the present study was undertaken to investigate a possible effect of the peptide on chloride reabsorption ( JCl ) in thick ascending limb ( TAL ) . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NEP inhibition was indicated by elevation of ANP and cGMP plasma concentrations in almost all subjects . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| However , the metabolic clearance of these hormones are dependent on similar systems , natriuretic peptide clearance receptor ( NPR C ) and neutral endopeptidase 24 . 11 ( NEP ) , suggesting a possible interaction between ANP and BNP on metabolic clearance . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| They include on the one hand the angiotensin converting enzyme ( ACE ) and endothelin converting enzyme ( ECE ) , on the other hand kinase 2 for bradykinin and neutral endopeptidase 24 . 11 ( NEP ) for ANP . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The present study was performed to examine the role of endogenous atrial natriuretic peptide ( ANP ) as a possible paracrine factor for cardiac fibroblasts , and to examine the effects of three neutral endopeptidase ( NEP ) inhibitors , thiorphan , phosphoramidon and ONO BB 039 02 ( ONO BB ) on endogenous ANP induced changes in collagen synthesis by cultured neonatal rat cardiac fibroblasts . 2 . ^^^ Our observations suggested that endogenous ANP released from cardiomyocytes inhibited collagen synthesis as a paracrine factor and that NEP inhibitors enhanced the activity of this peptide in cardiac fibroblasts . . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| CONCLUSION : These data indicate that the inhibition of NEP by thiorphan is able to ameliorate partially the reduction in GFR induced by CyA and to enhance , and prolong , the vasodilator and diuretic effects of ANP . . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase 24 . 11 ( NEP ) degrades substance P , kinins and atrial natriuretic peptide ( ANP ) , and aortic wall NEP activity was found to be increased in atherosclerosis . ^^^ Neutral endopeptidase 24 . 11 ( NEP ) degrades substance P , kinins and atrial natriuretic peptide ( ANP ) , and aortic wall NEP activity was found to be increased in atherosclerosis . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| OBJECTIVES : Neutral endopeptidase ( NEP ) inhibition potentiated the renal action of Atrial Natriuretic Peptide ( ANP ) and was associated with appearance of the peptide in the urine , providing evidence of protection of the filtrated peptide along the course of the nephron . ^^^ The hypothesis is that potentiation of urinary ANP by NEP inhibition could limit renin secretion by directly or indirectly targeting the macula densa in vivo . ^^^ METHODS AND RESULTS : We tested the interaction between NEP inhibition ( candoxatril ) and Na K 2Cl inhibition ( bumetanide ) on electrolyte and ANP urinary excretion , renin secretion , macula densa activity ( NADPH diaphorase activity and bNOS mRNA ) and TSC 1 mRNA expression in the renal cortex and BSC 1 in the renal medulla of rats treated for 5 days . ^^^ CONCLUSION : These results suggest that potentiation of ANP by NEP inhibition could interfere with tubular function at different levels and limit renin secretion by a urinary pathway involving macula densa activity . . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| OBJECTIVE : Increased secretion of atrial and brain natriuretic peptide ( ANP and BNP ) from hearts is known to exhibit favorable effects in patients and animals with heart failure , and inhibition of neutral endopeptidase ( NEP ) , an enzyme that degrades ANP and BNP , may further increase these peptide levels . ^^^ RESULTS : A single administration of ONO 9902 inhibited the plasma and kidney NEP activities and thereby further augmented the elevation of plasma ANP concentration in rats with CAL at the 1st week after the operation . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Phosphoramidon , a neutral endopeptidase inhibitor , shifted the apparent potency of ANP to values equivalent to that of BNP , suggesting these kidney cell / slices rapidly degrade ANP but not BNP . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Inhibition of NEP increases levels of atrial natriuretic peptide ( ANP ) , brain natriuretic peptide ( BNP ) of myocardial cell origin , and C type natriuretic peptide ( CNP ) of endothelial cell origin as well as bradykinin and adrenomedullin . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Increase in ANP and BNP , potentially beneficial , may be achieved by administration of neutral endopeptidase inhibitors , at present an unsettled therapeutic possibility . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| They function as a combined angiotensin converting enzyme ( ACE ) inhibitor and neutral endopeptidase ( NEP ) inhibitor , the latter of which potentiates the actions of atrial natriuretic peptide ( ANP ) by minimizing its degradation in the circulation . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NEP inhibition increased circulating endothelin 1 ( from 2 . 01 + / 0 . 1 to 2 . 90 + / 0 . 2 pmol / l ; P < 0 . 01 ) , atrial natriuretic peptide ( ANP ; from 21 . 5 + / 2 . 7 to 29 . 6 + / 3 . 7 pmol / l ; P < 0 . 01 ) , and the ANP second messenger cGMP . ^^^ ANP , possibly through a tubular action , enhances the natriuresis observed after NEP inhibition . . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| In contrast , atrial natriuretic peptide ( ANP ) is a potent vasorelaxant and diuretic agent , which is mainly degraded by neutral endopeptidase 24 . 11 ( NEP ) in vivo . ^^^ Thus , compounds that can suppress the biosynthesis of ETs by inhibiting endothelin converting enzymes ( ECEs ) , which catalyse the final step of post translational processing of the vasoconstrictors , while simultaneously potentiating the levels of ANP by inhibiting NEP may have novel therapeutic utility . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The effects on ECE 1 and NEP were assessed by determining the inhibition of big endothelin 1 ( big ET 1 ) induced increases in mean arterial pressure ( MAP ) and increases in plasma atrial natriuretic peptide ( ANP ) concentrations respectively , in conscious rats . ^^^ |
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| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The enzyme neutral endopeptidase ( NEP ; EC 3 . 4 . 24 . 11 ) cleaves several vasoactive peptides such as the atrial natriuretic peptide ( ANP ) . ^^^ In order to elucidate the loss of natriuretic and diuretic properties of ANP in CHF we analyzed activity , protein concentrations , mRNA and immunostaining of NEP in kidneys of different models of severe CHF in the rat . ^^^ The increased renal NEP protein expression and activity may lead to enhanced degradation of ANP and may contribute to the decreased renal response to ANP in heart failure . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| We tested the hypothesis that NEP inhibition could potentiate the effect of atrial natriuretic peptide ( ANP ) on PMN vascular cell interactions in vitro . ^^^ METHODS AND RESULTS : ANP alone and its potentiation by retrothiorphan , the NEP inhibitor , significantly inhibited superoxide , lysozyme , and matrix metalloproteinase ( MMP ) 9 release by N formyl Met Leu Phe stimulated PMNs . ^^^ Activated PMNs degraded exogenous ANP , which was prevented by NEP inhibition . ^^^ CONCLUSIONS : ANP potentiation by NEP inhibition could limit PMN activation and its consequences on vascular cells . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Vasopeptidase inhibitors ( VPI ) cause dual inhibition of ACE and neutral endopeptidase , the latter resulting in decreased atrial natriuretic peptide ( ANP ) breakdown and thus enhanced natriuresis . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Similar to ACE , NEP is an endothelial cell surface metalloproteinase that is involved in the degradation of several regulatory peptides , including the natriuretic peptides , and , thus , NEP inhibition augments vasodilatation and natriuresis through increased levels of atrial natriuretic peptide ( ANP ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Pharmacologically , increases in ANP and BNP can be accomplished with NEP inhibitors or beta blockers . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Many vasoactive peptides such as atrial natriuretic peptide ( ANP ) and endothelin 1 ( ET 1 ) are degraded by neutral endopeptidase 24 . 11 ( NEP ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Our present in vitro studies characterize the NEP dependent metabolism of ANP and BNP in different tissues via HPLC analysis using NEP deficient mice and specific NEP inhibitors . ^^^ Whereas NEP rapidly degraded ANP , it had no influence in BNP metabolism . ^^^ Moreover , we describe a degradation of ANP and BNP in NEP deficient and NEP inhibited membranes . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Relation of ANP and BNP to their N terminal fragments in fetal circulation : evidence for enhanced neutral endopeptidase activity and resistance of BNP to neutral endopeptidase in the fetus . ^^^ OBJECTIVES : To investigate the role of neutral endopeptidase in the turnover of atrial ( ANP ) and brain ( BNP ) natriuretic peptides and their N terminal fragments in human fetal circulation . ^^^ MAIN OUTCOME MEASURES : Maternal and fetal plasma concentrations of ANP , NT proANP , BNP , NT proBNP as well as neutral endopeptidase activity . ^^^ The ANP concentration is only 1 . 8 times higher , probably due to doubled neutral endopeptidase activity . ^^^ The results show that increased fetal neutral endopeptidase activity shifts the ANP / NT proANP but not the BNP / NT proBNP ratio and that the shifted BNP / NT proBNP ratio in fetuses with Rh isoimmunisation does not involve increased neutral endopeptidase activity . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| In this study we examined the activity of neutral endopeptidase ( NEP ) , an enzyme responsible for degradation of ANP , in the kidney in rats subjected to BUO for 24 hours . ^^^ Renal responses to an intravenous bolus injection of ANP ( 5 microg / kg ) were studied in sham operated and BUO rats with or without pretreatment with intravenous phosphoramidon ( 100 microg / kg per minute ) , a NEP inhibitor . ^^^ CONCLUSIONS : Renal responses to ANP and renal NEP activity were preserved in 24 hour BUO . ^^^ NEP inhibition to attenuate ANP degradation augmented responses to ANP in increasing GFR , natriuresis and diuresis . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| BACKGROUND : Neutral endopeptidase ( NEP ) degrades atrial natriuretic peptide ( ANP ) that via cyclic guanosine monophosphate ( cGMP ) is natriuretic and aldosterone inhibiting . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The enzyme neutral endopeptidase ( NEP ) degrades ANP and bradykinin and generates endothelin 1 from big endothelin . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Similar to ACE , NEP is an endothelial cell surface metalloproteinase , which is involved in the degradation of several regulatory peptides including the natriuretic peptides and thus augments vasodilatation and natriuresis through increased levels of atrial natriuretic peptide ( ANP ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| In addition , BNP ( 1 32 ) , BNP ( 3 32 ) , and ANP ( 1 28 ) were subjected to hydrolysis by NEP . ^^^ Under in vitro circumstances in which ANP was hydrolyzed extensively , BNP ( 1 32 ) and BNP ( 3 32 ) were very resistant to NEP mediated cleavage . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NEP is a cell surface metalloprotease that degrades several vasoactive peptides , including endothelin 1 ( ET 1 ) and atrial natriuretic peptide ( ANP ) . ^^^ Plasma ANP concentrations increased at HA in both genotypes , but plasma ET 1 concentrations were elevated only in the NEP null mice at HA . ^^^ We conclude that NEP null mice exposed to HA have a greater rise in ANP versus ET 1 plasma concentration , decreased pulmonary vascular pressure , and reduced high altitude induced pulmonary vascular leak . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The in vivo inhibition of ACE and NEP was monitored by measuring the urinary excretion of N acetyl Ser Asp Lys Pro ( AcSDKP ) and atrial natriuretic peptide ( ANP ) , respectively . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase degrades atrial natriuretic peptide ( ANP ) and bradykinin and may generate endothelin 1 from big endothelin . ^^^ In advanced cirrhosis , sodium retention is accompanied by elevated plasma ANP levels , and infusion of ANP causes hypotension , but in normal humans increasing the concentration of ANP through the inhibition of neutral endopeptidase , localized in renal proximal tubule cells , causes natriuresis without any arterial pressure drop . ^^^ In cirrhotic rats , Western blot analysis revealed a 170 % increase in renal neutral endopeptidase protein content ( P < 0 . 03 ) , mainly in the proximal nephron and macula densa , and both candoxatrilat dosages increased plasma ANP levels , urinary volume , and urinary excretion of sodium , ANP , and cGMP compared with vehicle alone ( all P < 0 . 03 ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase inhibitor , phosphoramidon , and ANP clearance receptor antagonist , C ANP , increased urinary ANP excretion in all groups to a similar level , but their natriuretic effect was impaired in obese and leptin treated groups . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| METHODS : We examined the interaction between angiotensin 2 ( Ang 2 ) and atrial natriuretic peptide ( ANP ) under low ( 5 mM ) and high ( 30 mM ) glucose conditions , on cell proliferation and extracellular matrix ( ECM ) synthesis in renomedullary interstitial cells ( RMICs ) derived from wild type ( WT ) and NEP deficient ( NEP ) mice . ^^^ ANP ( 10 ( 7 ) M ) reduced Ang 2 induced cell proliferation and ECM synthesis in RMICs derived from both strains , but more efficiently in RMICs derived from NEP mice . ^^^ CONCLUSIONS : This data shows that ANP and AT 1 receptor blockade attenuate Ang 2 induced RMIC proliferation and ECM synthesis more efficiently in the absence of NEP . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| BACKGROUND : The synergistic effects of the combined ACE and NEP inhibition is based both on the blockade of angiotensin 2 synthesis and degradation of vasoactive peptides and NEP substrates ( ANP , arginine , endothelial cells , guanylat cyclase etc . ) , including bradykinine and the natriuretic peptides , which contribute to vasodilatation , diuresis and improvement of myocardial function . ^^^ CONCLUSIONS : Two week treatment with the dual ACE / NEP inhibitor omapatrilat caused a significant decrease of the SBP , inhibition of the serum ACE activity and increase of the plasma ANP values , and therefore it should be considered as a new potential therapeutic agent in blood pressure management ( Tab . 3 , Fig . 2 , Ref . 20 ) . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Candoxatril , an orally active neutral endopeptidase inhibitor , raises plasma atrial natriuretic factor and is natriuretic in essential hypertension . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NEP plays a major role in the catabolism by these cells of atrial natriuretic factor . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Increased circulating atrial natriuretic factor concentrations in patients with chronic heart failure after inhibition of neutral endopeptidase : effects on diastolic function . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| C . 3 . 4 . 24 . 11 ) , also known as the common acute lymphocytic leukemia antigen , neutral endopeptidase , or enkephalinase , functions as an inactivator of a wide variety of signaling oligopeptides such as substance P , neurokinin A , enkephalins , endothelin , atrial natriuretic factor , and formyl chemotactic peptides . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The renal natriuretic actions of endogenous atrial natriuretic factor are enhanced by neutral endopeptidase inhibition ( NEP 1 ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Membrane metalloendopeptidase ( MMEP ; EC 3 . 4 . 24 . 11 ; enkephalinase ) catalyzes the degradation of endothelins , enkephalins , atrial natriuretic factor , substance P , and other small bioactive peptides . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The atriopeptidase inhibitor ( + / ) candoxatrilat reduces the clearance of atrial natriuretic factor in both intact and nephrectomized rats : evidence for an extrarenal site of action . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Atrial natriuretic factor is metabolized by neutral endopeptidase ( atriopeptidase ; EC 3 . 4 . 24 . 11 ) in vitro . ^^^ Inhibition of neutral endopeptidase ( EC 3 . 4 . 24 . 11 ) leads to an atrial natriuretic factor mediated natriuretic , diuretic and antihypertensive response in rodents . 1 . ^^^ Inhibitors of this enzyme have been reported to prolong the half life of atrial natriuretic factor in vivo and to potentiate the renal and haemodynamic effects of exogenous atrial natriuretic factor . 2 . ( + / ) Candoxatrilat , a selective neutral endopeptidase inhibitor , potentiated the natriuretic and diuretic response to volume loading in anaesthetized rats . ^^^ These data demonstrate that the neutral endopeptidase inhibitor ( + / ) candoxatrilat has natriuretic / diuretic and antihypertensive effects in rodents , and that these effects are mediated via endogenous atrial natriuretic factor . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Atriopeptidase ' ' ( EC 3 . 4 . 24 . 11 ) inhibition and protection of atrial natriuretic factor . ^^^ Atriopeptidase ' ' ( EC 3 . 4 . 24 . 11 ) inhibition and protection of atrial natriuretic factor . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| These modifications lead to CGS 25155 , an orally active NEP 24 . 11 inhibitor that slows down the degradation of the cardiac hormone atrial natriuretic factor , producing a lowering of blood pressure in the DOCA salt rat model of hypertension . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The acute effects of a single oral dose of sinorphan ( 100 mg ) , an inhibitor of neutral endopeptidase , on the plasma atrial natriuretic factor level and the fractional excretion of sodium were examined in 12 patients with severe chronic renal failure who were not on maintenance haemodialysis and who ingested a normal sodium diet . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Kinetic results obtained using a series of related substrates derived from biologically active peptides of the atrial natriuretic factor , tachykinin , and enkephalin families indicated the presence of an extended binding site accommodating at least six amino acid residues , in contrast to thermolysin ( EC 3 . 4 . 24 . 4 ) and neutral endopeptidase ( NEP ; EC 3 . 4 . 24 . 11 ) , which hydrolyze shorter homologous peptides . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| An interesting approach for the treatment of congestive heart failure and chronic hypertension could be to avoid the formation of angiotensin 2 by inhibiting angiotensin converting enzyme ( ACE ) and to protect atrial natriuretic factor by blocking neutral endopeptidase 24 . 11 ( NEP ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| If so , inhibition of atrial natriuretic factor breakdown by neutral endopeptidase ( NEP ) may enhance the antihypertensive effects of ACE inhibition . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase ( NEP , 24 . 11 ) is an ectoenzyme involved in the degradation of peptide hormones such as endothelin ( ET ) , atrial natriuretic factor and enkephalins . ^^^ Neutral endopeptidase ( NEP , 24 . 11 ) is an ectoenzyme involved in the degradation of peptide hormones such as endothelin ( ET ) , atrial natriuretic factor and enkephalins . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Degradation of atrial natriuretic factor in mouse blood in vitro and in vivo : role of enkephalinase ( EC 3 . 4 . 24 . 11 ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Depressor and renal activities of atrial natriuretic factor ( 99 126 ) were determined in conscious , unrestrained spontaneously hypertensive rats treated with a neutral endopeptidase inhibitor , SQ 29 , 072 ( 7 [ [ 2 ( mercaptomethyl ) 1 oxo 3 phenylpropyl ] amino ] heptanoic acid ) . ^^^ In summary , the neutral endopeptidase inhibitor SQ 29 , 072 increased the magnitudes and especially the durations of the depressor , natriuretic , and cyclic guanosine monophosphate responses to exogenous atrial natriuretic factor ( 99 126 ) in conscious spontaneously hypertensive rats , presumably by inhibition of degradation of atrial natriuretic factor in vivo . ^^^ In conclusion , neutral endopeptidase inhibition offers an important new technique for enhancement and prolongation of the biological lifetime of atrial natriuretic factor . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Clearance of brain natriuretic peptide in patients with chronic heart failure : indirect evidence for a neutral endopeptidase mechanism but against an atrial natriuretic peptide clearance receptor mechanism . 1 . ^^^ Two pathways of clearance for atrial natriuretic peptide are recognized : degradation by neutral endopeptidase and binding to atrial natriuretic peptide clearance receptors . ^^^ We have examined the effect of candoxatril , an inhibitor of neutral endopeptidase ( dose range 10 200 mg ) , and the effect of an infusion of a pharmacological dose [ 45 micrograms ( 90 micrograms in two patients ) ] of synthetic human atrial natriuretic peptide on plasma human brain natriuretic peptide like immunoreactivity levels in seven patients with mild to moderate chronic heart failure . 2 . ^^^ We have therefore shown that plasma human brain natriuretic peptide like immunoreactivity levels in chronic heart failure are increased by a neutral endopeptidase inhibitor , but are unchanged by an exogenous infusion of atrial natriuretic peptide . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The range of substrates cleaved by neutral endopeptidase in vitro includes the enkephalins , substance P , endothelin , bradykinin and atrial natriuretic factor . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The in vivo inhibition of angiotensin converting enzyme ( ACE ) and neutral endopeptidase ( NEP ) were monitored simultaneously by sequentially measuring the urinary excretion of N Acetyl Ser Asp Lys Pro and of the atrial natriuretic factor to compare the magnitude and the duration of action of a vasopeptidase inhibitor , omapatrilat , and an ACE inhibitor , fosinopril . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase ( NEP ) , a membrane bound metallopeptidase enzyme that degrades neuropeptides , bradykinin , atrial natriuretic factor , enkephalins , and endothelin may regulate response to injury . ^^^ Neutral endopeptidase ( NEP ) , a membrane bound metallopeptidase enzyme that degrades neuropeptides , bradykinin , atrial natriuretic factor , enkephalins , and endothelin may regulate response to injury . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase ( NEP ) is the major enzyme involved in the metabolic inactivation of a number of bioactive peptides including the enkephalins , substance P , endothelin , bradykinin and atrial natriuretic factor . ^^^ Neutral endopeptidase ( NEP ) is the major enzyme involved in the metabolic inactivation of a number of bioactive peptides including the enkephalins , substance P , endothelin , bradykinin and atrial natriuretic factor . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Inhibition of metabolizing peptidases such as aminopeptidase N and endopeptidase 24 . 11 ( NEP ) for enkephalins and of NEP and ACE for atrial natriuretic peptide and angiotensin 1 by mixed inhibitors such as kelatorphan and RB 101 or ES 14 , rationally designed by taking into account the structural differences in the active site of these zinc metallopeptidases , led to potent analgesics devoid of the major morphine side effects or to new antihypertensives . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase inhibitors lower blood pressure by inhibiting the metabolism of atrial natriuretic peptide and other vasoactive peptides . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Two metallopeptidases , angiotensin converting enzyme ( ACE ) and neutral endopeptidase ( NEP ) are involved respectively in the release of angiotensin 2 which is a vasoconstrictor , and in the metabolism of atrial natriuretic peptide which is diuretic and bradykinin which is a vasodilatator . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| This might perhaps be achieved in the future with the administration of neutral endopeptidase inhibitors which interfere with the enzymatic degradation of atrial natriuretic peptide . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Inhibitors of neutral endopeptidase will cause an accumulation of endogenous atrial natriuretic peptide , and hence lower blood pressure by counteracting several effects of the renin angiotensin system . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase 24 . 11 , also known as the common acute lymphoblastic leukemia antigen , is a zinc metallopeptidase involved in the inactivation of biologically active peptides , such as the enkephalins and atrial natriuretic peptide . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The common acute lymphoblastic leukemia antigen ( CALLA , CD 10 ) has been identified as neutral endopeptidase 24 . 11 ( NEP ) , a mammalian ectoenzyme involved in the inactivation of regulatory peptides , such as the enkephalins and atrial natriuretic peptide . ^^^ Six anti CALLA antibodies were found to inhibit 50 % or more of the hydrolysis of D Ala 2 leucine enkephalin by the neutral endopeptidase present on the human leukemic cell line Reh 6 and , to a lesser extent , the hydrolysis of atrial natriuretic peptide . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase 24 . 11 ( EC 3 . 4 . 24 . 11 ) inactivates atrial natriuretic peptide by cleaving the hormone between Cys 7 and Phe 8 , and inhibitors of the enzyme have consequent natriuretic and diuretic properties . ^^^ A 94 kDa protein , identified as neutral endopeptidase 24 . 11 , can inactivate atrial natriuretic peptide in the vascular endothelium . ^^^ Neutral endopeptidase 24 . 11 ( EC 3 . 4 . 24 . 11 ) inactivates atrial natriuretic peptide by cleaving the hormone between Cys 7 and Phe 8 , and inhibitors of the enzyme have consequent natriuretic and diuretic properties . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| In view of interest in the therapeutic potential of elevating plasma atrial natriuretic peptide by inhibition of neutral endopeptidase 24 . 11 , we studied the renal and hormonal effects of 200 mg of the oral endopeptidase 24 . 11 inhibitor candoxatril in eight patients with untreated essential hypertension on high sodium ( 350 mmol / day ) and low sodium ( 10 mmol / day ) diets . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase ( EC 3 . 4 . 24 . 11 , NEP ) is a Zn metallopeptidase involved in the degradation of biologically active peptides , notably the enkephalins and atrial natriuretic peptide . ^^^ Neutral endopeptidase ( EC 3 . 4 . 24 . 11 , NEP ) is a Zn metallopeptidase involved in the degradation of biologically active peptides , notably the enkephalins and atrial natriuretic peptide . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The role of neutral endopeptidase 24 . 11 and other proteases in regulating the effect of atrial natriuretic peptide on bronchial smooth muscle was also examined by studying the influence of phosphoramidon , a protease inhibitor , whose actions include the inhibition of neutral endopeptidase 24 . 11 , and the protease inhibitors leupeptin , aprotinin and soybean trypsin inhibitor on the airway response to atrial natriuretic peptide . 3 . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase 24 . 11 , a membrane bound metallopeptidase , cleaves , and degrades vasoactive peptides such as atrial natriuretic peptide , endothelin , angiotensin 1 , substance P , and bradykinin . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase 24 . 11 ( NEP ) is a membrane bound zinc metallopeptidase which cleaves biologically active peptides such as the enkephalins and atrial natriuretic peptide . ^^^ Neutral endopeptidase 24 . 11 ( NEP ) is a membrane bound zinc metallopeptidase which cleaves biologically active peptides such as the enkephalins and atrial natriuretic peptide . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Candoxatrilat , a neutral endopeptidase inhibitor , reduces degradation of atrial natriuretic peptide and provokes diuresis in patients with mild heart failure , but the renal effects have not been studied in patients with moderately severe heart failure in a placebo controlled study . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase ( NEP ) 24 . 11 is a zinc metallopeptidase involved in the metabolism of several biologically active peptides including enkephalin , atrial natriuretic peptide , bradykinin , and endothelin . ^^^ Neutral endopeptidase ( NEP ) 24 . 11 is a zinc metallopeptidase involved in the metabolism of several biologically active peptides including enkephalin , atrial natriuretic peptide , bradykinin , and endothelin . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The endogenous plasma concentration of alpha rat atrial natriuretic peptide ( alpha rANP ) in the MI rat was 6 . 4 fold higher than that in the normal rat , and intravenous infusion of phosphoramidon ( 165 nmol / min / kg ) , an NEP inhibitor , induced larger increases in circulating alpha rANP levels and natriuresis in MI rats than in normal controls . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| A novel fluorogenic peptide , dansyl Gly ( p NO 2 ) Phe beta Ala ( DGNPA ) , was synthesized as a selective substrate for neutral endopeptidase 24 . 11 , an enzyme involved in enkephalin and atrial natriuretic peptide degradation and a marker of differentiation ( CD 10 ) on the surface of lymphohematopoietic cells . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Plasma concentrations of endogenous alpha rat atrial natriuretic peptide ( alpha rANP ) were not significantly elevated by intravenous infusion of a NEP inhibitor , phosphoramidon , but were elevated threefold by intravenous infusion of a clearance receptor ligand , des ( Gln 18 Gly22 ) rANP ( 4 23 ) NH 2 [ C ANF ( 4 23 ) ] . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Acute pharmacological inhibition of the enzyme neutral endopeptidase ( EC 3 . 4 . 24 . 11 ) , which cleaves the cardiac hormone atrial natriuretic peptide , raises endogenous levels of the hormone . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| RESULTS : Inhibition of neutral endopeptidase by 10 , 30 , or 100 mumol . kg 1 SQ 28 , 603 given intravenously increased sodium excretion , cyclic GMP excretion , and plasma concentrations of atrial natriuretic peptide in a dose related manner in conscious dogs paced for one week . ^^^ CONCLUSIONS : Inhibition of neutral endopeptidase in dogs with pacing induced heart failure protected endogenous atrial natriuretic peptide from degradation and stimulated sustained natriuresis , presumably via a tubular mechanism . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NEP cleaves a variety of peptides including bradykinin , substance P , bombesin , enkephalins , and atrial natriuretic peptide . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| A role for neutral endopeptidase 24 . 11 ( NEP ) in growth and development is supported by the demonstration that NEP hydrolyses and inactivates a number of peptide growth factors including atrial natriuretic peptide , endothelins , bombesin like peptides , and opioid peptides , including the enkephalins . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Endothelial neutral endopeptidase ( EC 3 . 4 . 24 . 11 , NEP ) contributes to the inactivation of vasoactive and inflammatory peptides such as f Met Leu Phe , substance P , atrial natriuretic peptide , and bradykinin . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Therefore , the vascular responses to combined NEP and ACE inhibitors did not necessarily depend upon increases in circulating atrial natriuretic peptide or reductions in angiotensin 2 levels . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Atrial natriuretic peptide is degraded in part by a neutral endopeptidase . ^^^ We determined the effect of neutral endopeptidase inhibition on plasma levels of atrial natriuretic peptide and the renal response to acute volume expansion in rats with aortocaval shunts and in sham operated controls . ^^^ In contrast to the acute effects , chronic neutral endopeptidase inhibition with SCH 34826 ( 30 mg / kg twice daily ) in shunted rats did not change atrial natriuretic peptide plasma levels or cGMP excretion . ^^^ Our data show that the renal effects of neutral endopeptidase inhibition are not necessarily dependent on changes in atrial natriuretic peptide plasma levels but instead may be mediated by local inhibition of the neutral endopeptidase in the kidney . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Increasing circulating levels of atrial natriuretic peptide via neutral endopeptidase inhibition may offer an alternative way to increase diuresis and natriuresis without neuroendocrine stimulation . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Plasma atrial natriuretic peptide and brain natriuretic peptide were significantly higher in RHR 1 and RHR 2 than in Sham 1 , Sham 2 and NEP . ^^^ Atrial natriuretic peptide and brain natriuretic peptide mRNA levels of NEP were normalized . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Inhibition of endopeptidase EC 3 . 4 . 24 . 11 by candoxatril lowered blood pressure and increased urinary but not plasma atrial natriuretic peptide in essential hypertension . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Accordingly , the potency of novel inhibitors against NEP and ACE were determined in conscious monkeys by the potentiation of the natriuretic activity of exogenous human atrial natriuretic peptide and inhibition of the pressor response to angiotensin 1 , respectively . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| A wide range of biologically active peptide substrates has been described for NEP , of which the enkephalins and the atrial natriuretic peptide family have assumed greatest significance . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Inhibition of neutral endopeptidase ( NEP ) , the degradative enzyme for atrial natriuretic peptide , was studied in vitro and in vivo using a previously characterized NEP inhibitor radioligand , 125I labelled RB 104 . 2 . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Two of the three angiotensin forming enzymes ( neprilysin and endopeptidase 24 . 15 ) also contribute to the breakdown of bradykinin and the atrial natriuretic peptide . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase 24 . 11 ( NEP ) is localized in greatest abundance in the kidney and cleaves endogenous peptides like atrial natriuretic peptide , which also possesses a disulfide ring . ^^^ Neutral endopeptidase 24 . 11 ( NEP ) is localized in greatest abundance in the kidney and cleaves endogenous peptides like atrial natriuretic peptide , which also possesses a disulfide ring . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Effect of neutral endopeptidase inhibition on the natriuresis and renal clearance of atrial natriuretic peptide in perfused rat kidney . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Candoxatril is an inhibitor of neutral endopeptidase , a membrane bound enzyme that degrades atrial natriuretic peptide . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The cardiac natriuretic peptides , atrial natriuretic peptide and brain natriuretic peptide , are degraded via clearance receptors and the enzyme neutral endopeptidase ( EC 3 . 4 . 24 . 11 ) . ^^^ The transcardiac step up in atrial natriuretic peptide was markedly augmented after the administration of neutral endopeptidase inhibitor . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Whereas endogenous levels of atrial natriuretic peptide are increased by neutral endopeptidase inhibition in most pathophysiological states , the effect on brain natriuretic peptide and the influence of cardiac status is less clear . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| This suggests that bronchodilator NEP substrates , such as vasoactive intestinal polypeptide or atrial natriuretic peptide , modulate EIB in patients with asthma . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Both neprilysin and thimet oligopeptidase are also involved in the metabolism of bradykinin and the atrial natriuretic peptide . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Both neprilysin and thimet oligopeptidase are also involved in the metabolism of bradykinin and the atrial natriuretic peptide . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Both neprilysin and metalloendopeptidase 24 . 15 form Ang ( 1 7 ) but also cleave bradykinin and atrial natriuretic peptide to smaller fragments . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The differences appear to be due , at least in part , to increased renal exposure to atrial natriuretic peptide following neutral endopeptidase blockade . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| In the kidney , NEP is implicated in the degradation of regulatory factors involved in the control of arterial pressure , including atrial natriuretic peptide and bradykinin . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Omapatrilat , but not captopril , significantly increased urinary atrial natriuretic peptide excretion , indicating NEP inhibition . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| The principal effect of ecadotril on distal tubular sodium reabsorption suggests that inhibition of NEP activity in the proximal renal tubules may allow increased binding of filtered atrial natriuretic peptide to natriuretic peptide receptor sites in the distal renal tubules and collecting ducts . . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Similar to ACE , NEP is an endothelial cell surface metalloproteinase , which is involved in the degradation of several regulatory peptides including the natriuretic peptides , and augments vasodilatation and natriuresis through increased levels of atrial natriuretic peptide . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NEP metabolizes both bradykinin and the natriuretic peptides ( atrial natriuretic peptide , brain natriuretic peptide , c type natriuretic peptide and adrenomedullin ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Compared with captopril , S 21402 increased levels of plasma atrial natriuretic peptide ( P < . 05 ) and urinary cyclic guanosine monophosphate ( P < . 001 ) ; these increases were the result of inhibition of neutral endopeptidase activity ( P < . 001 ) . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| In hearts from citrate treated control rats , angiotensin 2 stimulated [ ( 3 ) H ] phenylalanine incorporation and atrial natriuretic peptide and beta myosin heavy chain mRNA expression were prevented by B type natriuretic peptide ( BNP ) , bradykinin , the ACE inhibitor ramiprilat , and the neutral endopeptidase inhibitor candoxatrilat . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Inhibition of neutral endopeptidase activity was shown by increases in the daily urinary excretion of atrial natriuretic peptide and cyclic guanosine monophosphate at doses of more than 7 . 5 and 25 mg , respectively . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| In the kidney , neutral endopeptidase ( NEP ) is implicated in the metabolism of several peptides involved in blood pressure and sodium homeostasis control , such as the atrial natriuretic peptide , bradykinin and angiotensin 1 . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| As ACE and NEP catalyse degradation of the permeability increasing peptide bradykinin , and NEP also catalyses degradation of permeability increasing peptides such as atrial natriuretic peptide , substance P , endothelin 1 and angiotensin 2 , vasopeptidase inhibition may increase microvascular permeability . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Neutral endopeptidase 24 . 11 breaks down both atrial natriuretic peptide and angiotensin 2 . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| Omapatrilat combines the action of an ACEI and of an inhibitor of a neutral endopeptidase involved in the metabolism of the atrial natriuretic peptide . ^^^ |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01160 and P08473 |
Pubmed |
SVM Score :0.0 |
| NA |
|