Effects of angiotensin-II receptor blocker candesartan cilexetil in rats with dilated cardiomyopathy

We examined effects of an angiotensin-II receptor blockers, candesartan cilexetil, in rats with dilated cardiomyopathy after autoimmune myocarditis. Candesartan cilexetil showed angiotensin-II blocking action in a dose-dependent manner in rats with dilated cardiomyopathy. Twenty-eight days after immunization, surviving Lewis rats were divided into four groups and given candesartan cilexetil at 0.05 mg/kg, 0.5 mg/kg or 5 mg/kg per day (Group-C0.05, n = 15, Group-C0.5, n = 15 and Group-C5, n = 15, respectively) or vehicle alone (Group-V, n = 15). After oral administration for 1 month, the left ventricular end-diastolic pressure and heart weight/body weight ratio were lower in Group-C0.05 (13.3 +/- 1.1 mmHg and 3.7 +/- 0.2 g/kg, respectively), in Group-C0.5 (8.0 +/- 0.9 mmHg and 3.3 +/- 0.1 g/kg, respectively) and in Group-C5 (5.5 +/- 1 mmHg and 3.1 +/- 0.1 g/kg, respectively) than in Group-V (13.5 +/- 1.0 mmHg and 3.8 +/- 0.2 g/kg, respectively). The area of myocardial fibrosis was also lower in Group-C0.05 (25 +/- 3%), in Group-C0.5 (20 3%), and in Group-C5 (12 +/- 1%) than in Group-V (32 +/- 4%). Furthermore, expressions of transforming growth factor-beta1 and collagen-III mRNA were suppressed in Group-C0.05 (349 +/- 23% and 395 +/- 22%, respectively), Group-C0.5 (292 +/- 81% and 364 +/- 42%, respectively) and in Group-C5 (204 +/- 63% and 259 +/- 33%, respectively) compared with those in Group-V (367 +/- 26% and 437 +/- 18%, respectively). These results suggest that candesartan cilexetil can improve the function of inefficient heart.