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.(ABSTRACT TRUNCATED AT 250 WORDS)