Beneficial Renal and Cardiac Effects of Vasopeptidase Inhibition With S21402 in Heart Failure

Publisher Website
Google Scholar
Abstract
S21402 is a vasopeptidase inhibitor that simultaneously inhibits neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE). This study determined whether chronic treatment with S21402 produced different effects on sodium and water excretion, hormonal parameters, and cardiovascular structure compared with selective inhibition of ACE and NEP in a rat model of myocardial infarction–induced congestive heart failure (CHF). CHF rats received the vasopeptidase inhibitor (S21402, 100 mg · kg − 1 · d − 1 ), an ACE inhibitor (captopril, 50 mg · kg − 1 · d − 1 ), a NEP inhibitor ( SCH42495 , 60 mg · kg − 1 · d − 1 ), or vehicle for 4 weeks. S21402 alone caused a diuresis and natriuresis ( P P P P P P P P P P P P P <0.01). In CHF, vasopeptidase inhibition with S21402 produces effects that differ from those of selective NEP or ACE inhibition. S21402 improved sodium and water excretion, reduced pulmonary congestion, and attenuated both right and left ventricular remodeling. These effects, which occurred in the absence of any hypotensive action, suggest that S21402 may offer several advantages over ACE inhibition alone in the treatment of heart failure.