Role of renin-angiotensin system in the pathogenesis of spontaneous myocardial fibrosis in Sprague-Dawley rats: effect of long-term administration of captopril.

Abstract

The role of endogenous renin-angiotensin system in the pathogenesis of spontaneous myocardial fibrosis in male and female Sprague-Dawley rats was examined by long-term inhibition of endogenous angiotensin II production. For this purpose captopril, angiotensin I converting enzyme inhibitor (ACEI), was given at 30 or 100 mg/kg/day mixed with commercial powdered standard diet (CE-2, Japan Clea Co., Tokyo) for 52 weeks. Myocardial lesions consisting of focal fibrosis and minute necrotic foci of muscle cells intermingled with monocytic infiltration appeared preferentially in the subendocardial areas of the left ventricle. The incidence of myocardial fibrosis was very low in female rats, but in male rats, the incidence and severity of the lesion was significantly reduced in the captopril-treated groups than in the control group. These findings suggest that endogenous angiotensin II acts as a facilitatory effect on the pathogenesis of spontaneous myocardial lesion which can be effectively reduced by long-term administration of nontoxic dose of ACEI. The authors speculate that ACEI may have a therapeutic use in clinical cases of idiopathic myocarditis.