Efficacy of Angiotensin-Converting Enzyme Inhibition and AT1 Receptor Blockade on Cardiac Pump Performance After Myocardial Infarction in Rats

Abstract

Summary: To determine whether cardiac unloading by inhibition of angiotensin I (AI) to AII conversion by captopril or blockade of the AII receptor (AT₁) by losartan was more effective in prevention of the detrimental hemodynamic consequences of myocardial infarction (MI), inhibition of metabolic production of AII by captopril was compared with blockade of AT₁ with losartan in Sprague-Dawley rats with large MI. Infarcts were created by surgical occlusion of the left main coronary artery and oral drug therapy initiated immediately and continued until hemodynamic evaluation seven days later. Heart weight was unchanged in untreated infarcted animals, whereas captopril reduced heart weight in control animals and losartan increased heart weight in infarcted animals. Left ventricular (LV) peak systolic blood pressure (SBP) was lower in treated and untreated infarcted animals. Although captopril reduced end-diastolic pressure (EDP) to a greater degree than losartan, all infarcted group showed an increase in this parameter with respect to similarly treated controls. LV peak rates of pressure increase and decay in infarcted hearts were decreased significantly more by captopril than by losartan administration. Captopril also impaired right side cardiac function more than losartan when peak rate of pressure increase was evaluated. Thus, inhibition of the effects of AII during cardiac failure improved but did not normalize cardiac pump performance. Although inhibition of AII production by captopril produced its beneficial effect by reducing diastolic BP (DBP) and SBP, preventing AII binding by administration of losartan appeared to elicit its therapeutic effect by an improvement in myocardial contractility.