Effects of candesartan cilexetil on experimental congestive heart failure in rats and dogs

Abstract

Angiotensin II (All), effector molecule of renin-angietensin system (RAS), plays a substantial role in congestive heart failure (CHF) is well documented. We studied that the effect of All receptor antagonist, candesartan cilexetil (CC), in two experimental CHF models; rapid ventricular pacing (260 b.p.m., 42 days) in dogs and coronary ligated rats (20 weeks after ligation). In CHF dogs, oral treatment of CC at 10 mg/kg/day during pacing period suppressed the increase in plasma aldosterone and reduced the increase in right atrial pressure (RAP). Together with a lower RAP, the incidence in pleural effusion and ascites was also reduced in CC treated dogs. CC prevented the death with severe congestion in this model. In CHF rats, oral treatment of CC was started at 1 week after coronary ligation. At 20 weeks after ligation, CC at 10 mg/kg/day suppressed the increase in left ventricular end diastolic pressure, LV cavity dimension and weight. These results suggest that CC has benefitial effects on CHF resulting from prevention of congestion and cardiac remodeling. 006