Vasopeptidase inhibition with omapatrilat improves cardiac geometry and survival in cardiomyopathic hamsters more than does ACE inhibition with captopril.

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Trippodo NC, Fox M, Monticello TM, Panchal BC, Asaad MM

Vasopeptidase inhibition with omapatrilat improves cardiac geometry and survival in cardiomyopathic hamsters more than does ACE inhibition with captopril.

J Cardiovasc Pharmacol. 1999 Dec;34(6):782-90.

PubMed ID

10598120 [ View in PubMed

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Abstract

Vasopeptidase inhibitors are single molecules that inhibit neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) simultaneously. Omapatrilat, the first in this new class of cardiovascular agents, potentiates vasodilatory and cardioprotective peptides and represses angiotensin II. This study compared the effects of omapatrilat with those of a pure ACE inhibitor on cardiac geometry and survival in animals with heart failure. BIO TO-2 cardiomyopathic hamsters (CMHs) in the early stages of dilated heart failure were treated with vehicle or maximal ACE inhibitory doses of captopril (750 micromol/kg/day) or omapatrilat (200 micromol/kg/day). Prolonged vasopeptidase inhibition increased median survival time after the start of treatment by 99 and 31% compared with vehicle and captopril, respectively (median survival times: 146, 221, and 290 days with vehicle, captopril, and omapatrilat, respectively; p < 0.001 for all comparisons). In similar CMHs, captopril or omapatrilat administered for 2 months significantly (p < 0.05) decreased heart weight, pulmonary congestion (lung weight), and left ventricular (LV) chamber volume compared with vehicle. Omapatrilat significantly increased LV mass-to-volume ratio compared with vehicle and captopril. Omapatrilat, but not captopril, significantly increased urinary atrial natriuretic peptide excretion, indicating NEP inhibition. Thus vasopeptidase inhibition with omapatrilat was more effective than ACE inhibition with captopril in preventing changes in LV geometry and premature mortality in hamsters with dilated heart failure.

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Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Omapatrilat	Angiotensin-converting enzyme	Protein	Humans	Unknown	Not Available	Details