Effect of enalaprilic acid on cardiac contractile response to beta-adrenergic stimulation.
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 beta-adrenergic stimulation remained depressed. In the present study, we evaluate the contractile response to beta-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/mm2) and the cross-sectional area (mm2) 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 less than 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 beta-adrenergic stimulation. The inhibition of the local angiotensin II does not seem to be involved in this result.
Gomez Llambi
H
H
Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Taquini
C M
CM
Mazzadi
A
A
Gallo
A
A
Fontan
M
M
Taquini
A C
AC
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D015773:Enalaprilat / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000318:Adrenergic beta-Agonists; D000804:Angiotensin II; D015773:Enalaprilat; D007545:Isoproterenol