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

Abstract

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.

Candesartan improves myocardial damage in obese mice with viral myocarditis and induces cardiac adiponectin

“…These results suggest that hypoadiponectinemia is related to myocardial injury in obese mice with acute viral myocarditis. The AT1-receptor blocker reduced cardiac fibrosis, inflammation and increased adiponectin concentrations [15,23,24]. In our study, administration with candesartan significantly increased adiponectin concentrations and decreased severity of myocardial injury associated with the attenuation of cardiac hypertrophy and inflammation in obese mice with acute viral myocarditis.…”

Telmisartan, an angiotensin-II receptor blocker ameliorates cardiac remodeling in rats with dilated cardiomyopathy

“…We have previously reported that candesartan treatment reduced mortality, heart weight (HW), myocardial fibrosis and mRNA expressions of TGF-b1, and improved the survival rate and cardiac function in rats with DCM after myocarditis in a dose-dependent manner. 11 So far, only a few studies have investigated the effects of AT 1 R blockade in experimental myocarditis. 12 It is therefore important to determine the effect of ARBs on fetal gene expression or extracellular matrix (ECM) remodeling in models not only with heart failure after myocardial infarction, but also with DCM.…”

Oral Administration of Candesartan Improves the Survival of Mice with Viral Myocarditis through Modification of Cardiac Adiponectin Expression

“…Recently, we and others have reported that treatment with angiotensin II type1 blockers (ARB) reduces viral-mediated myocardial injury [3,4]. ARB has been shown to have antiinflammatory properties in vitro and animal studies.…”