In this study the effect of the
angiotensin converting enzyme (
ACE) inhibitor captopril on beta-receptor responsiveness was investigated in failing rat hearts after experimental
myocardial infarction. Infarcted rats were treated for 8 weeks with either
captopril added to the
drinking water (100 mg/kg/day; n = 5) or
drinking water alone (n = 7). Treatment was started 2-3 days before
myocardial infarction. A third group of untreated rats without
myocardial infarction served as control (n = 6). At the end of the treatment period the hearts were perfused as described by Langendorff, and a cumulative dose-response curve of
isoprenaline was obtained in each heart. In comparison with noninfarcted hearts, the response of heart rate and peak pressure rate (dP/dt) to
isoprenaline stimulation was significantly depressed in hearts of infarcted rats. Chronic treatment with
captopril significantly attenuated the reduced responsiveness to
isoprenaline stimulation. This improved responsiveness in
captopril-treated rat hearts might be due to prevention of "down-regulation" of myocardial beta-
adrenoceptors. Other factors should also be considered, such as prevention of structural alterations in the noninfarcted myocardium, e.g., myocardial
hypertrophy and
fibrosis. Differences in
infarct size did not play an important role, since
infarct size was comparable in both groups of infarcted rats. This partial preservation of beta-
adrenergic responsiveness was accompanied by a significant reduction in right ventricular weight and lung weight, suggesting that
captopril also improved the signs of
heart failure. Therefore, the results of this study indicate that early ACE inhibition in
myocardial infarction may be useful in preventing deterioration of cardiac function.