The cardioprotective properties of pranidipine were studied in a rat model of heart failure after autoimmune myocarditis. Twenty-eight days after immunization the surviving rats were divided into three groups and received oral treatment of 0.03 mg/kg/day (group 0.03) or 0.3 mg/kg/day (group 0.3) of pranidipine or vehicle (group V) for 1 month. High-dose pranidipine (group 0.3) improved the survival rate, and significantly reduced heart weight, heart weight to body weight ratio, myocardial fibrosis, central venous pressure and left ventricular end-diastolic pressure than low-dose pranidipine (group 0.03) and group V. Pranidipine at high dose also decreased the left ventricular systolic and diastolic dimensions, and increased fractional shortening compared with group V. The increase in level of TGF-beta1 and collagen-III mRNA were suppressed by pranidipine in a dose-dependent manner. Our results indicated that pranidipine has cardioprotective effects on heart failure, and that the beneficial effect can be partly explained by attenuation of fibrotic response through suppression of TGF-beta1 and collagen-III mRNA expression, and regression of myocyte hypertrophy.
Copyright 2004 S. Karger AG, Basel