Effect of enalaprilic acid on cardiac contractile response to β-adrenergic stimulation

Abstract

Studies in two-kidney-one clip hypertensive rats have demonstrated that long-term treatment with enalapril induced regression of cardiac hypertrophy, but the cardiac contractile response to β-adrenergic stimulation remained depressed. In the present study, we evaluate the contractile response to β-adrenergic stimulation of isolated papillary muscle in normal rats with isoproterenol (10 −11 M to 10 −4 M) in the presence of enalaprilic acid (10 −6 M or 10 −4 M) or enalaprilic acid (10 −4 M) and angiotensin II (10 −6 M). Myocardial contractility was characterized by maximal developed tension and maximal rate of rise of tension (+T), and the relaxant effect of isoproterenol by the ratio of (+T), and the maximal velocity of relaxation (-T)(+T/−T ratio). The rest tension (g/mm 2) and the cross-sectional area (mm 2) were similar in all the muscles studied. Enalaprilic acid (either 10 −6 M or 10 −4 M) in the bath did not induce any change in contractile and relaxation parameters. The increment in +T and –T (expressed as percentage) in response to cumulative doses of isoproterenol (10 −11 M to 10 −4 M) was significantly depressed in the presence of enalaprilic acid (10 −4 M) when compared with control hearts in which only vehicle was added before isoproterenol (p < 0.05). The addition of angiotensin II after enalaprilic acid (10 −4 M) did not normalize the response in +T and –T. Enalaprilic acid diminishes the contractile response of the papillary muscle to β-adrenergic stimulation. The inhibition of the local angiotensin II does not seem to be involved in this result. © 1990 American Heart Association, Inc.