Activation of the cardiac angiotensin-converting enzyme after myocardial infarction and its role in ventricular remodeling

To determine angiotensin converting enzyme (ACE) activity in the heart of infarcted rats and to investigate the effects of captopril and losartan on the post-infarction remodeling process. Myocardial infarction (MI) was produced in Wistar rats by ligature of the left coronary artery. Control rats (Con) underwent a sham surgery. MI and Con rats remained untreated or were treated with captopril (30 mg/kg/day) or losartan (15 mg/kg/day) for 30 days. ACE activity was determined in right (RV) and left ventricular (LV) muscles and in the scar tissue. The effects of captopril therapy was also investigated in the hydroxiproline (OH-Pro) and protein in RV and LV. ACE activity increased 25% in the RV and 70% in the remaining LV muscle. The highest ACE activity was found in the scar tissue, where it was 4.5 times the value of the LV muscle (420 +/- 68 vs 94 +/- 8 nmoles/g/min; P < 0.01). An increase of the end-diastolic pressure and of the muscle mass was found in the RV and LV of MI rats. Captopril and losartan treatments were equally efficient to attenuate these parameters in both ventricles. Captopril also reduced the total OH-Pro content in the RV and LV muscles. The Prot concentration was significantly reduced in the myocardium of MI rats, an effect enhanced by captopril therapy. The AII concentration in the blood draining from the scar to the surrounding muscle is probably high. It is likely that this elevated local generation of AII contributes to hypertrophy and to collagen deposition. The effects of ACE inhibitors on remodeling are likely to depend on the reduction of the locally generated AII.