Hemodynamic effects of direct angiotensin ii blockade compared to converting enzyme inhibition in rat model of heart failure

Abstract

The purpose of this investigation was to compare the chronic effects of converting enzyme inhibition with captopril to direct blockade of angiotensin II (All) with DuP 753 in the rat model of heart failure. Rats with chronic heart failure postinfarction were treated for 2 weeks with either captopril (2 g/L, N = 9) in their drinking water or with DuP 753 (40 mg/kg/day for two weeks by gastric gavage, N = 10), or placebo (N = 9). At this dose, DuP 753 shifted the log dose-pressor response curve to All parallel to the right by two orders of magnitude in both chronically treated normal and heart failure rats. In rats with heart failure, DuP 753 and captopril re­duced left ventricular end-diastolic pressure from 26.7 ± 1.5 to 14.2 ± 3.0 (P