Coronary vascular remodeling and myocardial fibrosis in the rat with renovascular hypertension. Response to captopril

Abstract

Progressive myocardial fibrosis, including the accumulation of collagen within the adventitia of intramyocardial coronary arteries, is seen in the hypertrophied rat myocardium secondary to renovascular hypertension (RHT) and has been held responsible for alterations in myocardial diastolic stiffness. This study was undertaken to test the hypothesis that this presumptive angiotensin-aldosterone mediated fibrosis and its functional consequences could be favorably altered by an antihypertensive oral dose (50 mg/kg/day) of the angiotensin converting enzyme (ACE) inhibitor captopril. Three groups were studied: control; untreated RHT for 8 weeks; treated RHT, with captopril started 48 h before banding and continued for 8 weeks. Interstitial collagen volume fraction and perivascular collagen area (morphometry), the fibrillar nature of collagen (picrosirius polarization), and the end diastolic stress-strain relation of the intact left ventricle were examined in each group. In comparison to untreated animals with RHT, we found that captopril, begun prior to banding, attenuated interstitial and perivascular fibrosis and prevented hypertrophy and the rise in diastolic stiffness 8 weeks later. Thus, an adverse accumulation of collagen in the interstitium and around intramyocardial coronary arteries, and its functional consequences in the rat with RHT, can be prevented by captopril. Other ACE inhibitors may have similar salutary effects, but remain to be evaluated. The pathogenetic origin of myocardial fibrosis in RHT requires further investigation, but appears to be related to the angiotensin-aldosterone system.