Comparison between angiotensin receptor antagonism and converting enzyme inhibition in heart failure - Differential acute effects according to the renin-angiotensin system activation

This study was designed to assess the influence of the activation status of the renin angiotensin system (RAS) on the hemodynamic effects of EXP 3174 (an angiotensin AT1 receptor antagonist) and enalaprilat (an angiotensin co nverting enzyme inhibitor) in tachycardia-induced heart failure. Thirteen d ogs were chronically instrumented to measure left ventricular (LV) pressure , its first time derivative (LV dP/dt), atrial and aortic pressures, and ca rdiac output. EXP 3174 (0.1 mg/kg, iv) or enalaprilat (I mg/kg, iv) were ad ministered in conscious does with heart failure induced by right ventricula r pacing (250 beats/min, 3 weeks). EXP 3174 and enalaprilat produced signif icant vasodilation but tho effects of EXP 3174 on mean aortic pressure (MAP !, cardiac output, and total peripheral resistance (TPR) were only 50 % of those produced by enalaprilat. When does were grouped according to their ba seline plasma renin activity (PRA) values, in dogs with normal PRA (0.5 +/- 0.1 ng/ml/h) EXP 3174 did not produce significant change in MAP and TPR? w hile enalaprilat decreased significantly MAP and TPR. In contrast, in dogs with high PRA (6.7 +/- 3.2 ng/ml/h), EXP 3174 produced significant reductio ns in MAP and TPR, which were similar to those produced by enalaprilat. Thu s, in conscious does with heart failure, enalaprilat is effective whether t he RAS is activated or not. In contrast, EXP 3174 is effective only when th e RAS is activated. These results may help in the choice of inhibitors of t he RAS in heart failure.