Renal and depressor activities of inhibitors of neutral endopeptidase and angiotensin converting enzyme in monkeys infused with angiotensin II

Journal of Cardiovascular Pharmacology
A A SeymourC R Dorso

Abstract

In a previous study, the depressor activity of combined selective inhibitors of neutral endopeptidase EC 3.4.24.11 (NEP) and angiotensin-converting enzyme (ACE) depended on the level of ACE inhibition, whereas the renal responses were determined by NEP inhibition. Our study confirmed that a mixed NEP/ACE inhibitor BMS-182657 ([S-(R*,R*)]-2,3,4,5-tetrahydro-3-[(2-mercapto-1-oxo-3- phenylpropyl)amino]-2-oxo-1H-benzazepine-1-acetic acid) reduced mean arterial pressure (MAP) when renin release was reduced by a sodium load, suggesting that the depressor response did not require suppression of endogenous angiotensin II generation. Furthermore, a pressor dose of 30 ng/min of angiotensin II was required to block the depressor response to BMS-182657 in the presence or absence of exogenous human atrial natriuretic peptide (hANP 99-126). Thirty ng/min of angiotensin II also significantly enhanced the natriuresis induced by hANP 99-126 after BMS-182657 administration. In contrast, a nonpressor dose of angiotensin II (3 ng/min) reduced basal sodium excretion and the natriuretic responses to exogenous hANP 99-126 in the presence or absence of BMS-182657. The potentiation of the urinary ANP and cyclic guanosine monophosphate (cGMP) responses ...Continue Reading

References

May 1, 1992·Kidney International·D de ZeeuwP E de Jong
Oct 1, 1991·Canadian Journal of Physiology and Pharmacology·A A SeymourW L Rogers
Mar 1, 1991·Journal of Cardiovascular Pharmacology·A A SeymourB Abboa-Offei
Sep 1, 1991·Journal of Cardiovascular Pharmacology·N C TrippodoW L Rogers
Jul 1, 1987·The American Journal of Physiology·J B Smith, T M Lincoln
Jan 1, 1986·Kidney International·A G Scicli, O A Carretero
Jan 1, 1986·Chemical & Pharmaceutical Bulletin·Y ShimamoriY Fujimoto

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