Cardiovascular responses to the stereoisomers of dobutamine in isolated rat hearts 48 hours after acute myocardial infarction.
Effects of acute myocardial infarction (48 h) on cardiovascular responses to (+/-)-, (-)-, and (+)-dobutamine were studied in isolated perfused rat hearts. The effects of the racemate and the isomers on ventricular pressure were measured simultaneously in infarcted left ventricle and noninfarcted right ventricle. Administration of (+/-)-, (-)-, and (+)-dobutamine resulted in dose-dependent increases in inotropic parameters and coronary flow (CF) in both control and in infarcted hearts. As compared with the (+)-isomer, the racemate and the (-)-isomer in both control and infarcted hearts were approximately 1.5 and 15 times weaker with respect to inotropic parameters. For (+/-)-, (-)-, and (+)-dobutamine, there was no significant difference in pD2 values in any of the inotropic measurements between the infarcted group and the corresponding control group. The maximal obtainable responses were significantly lower in the infarcted groups as compared with their corresponding control group. In control hearts, effects of isoproterenol and methoxamine as compared with (+/-)-dobutamine were approximately 2 log units more and 2 log units less in potency, respectively. The inotropic effects of (-)-dobutamine but not those of methoxamine were completely antagonized by propranolol (0.3 microM). Although the results provide evidence for the existence of myocardial alpha 1-adrenoceptors, all forms of dobutamine exerted positive inotropic effects through activation of beta-adrenoceptors both in control and in infarcted in rat hearts.
Vleeming
W
W
Department of Pharmacotherapy, Faculty of Pharmacy, University Utrecht, The Netherlands.
van Rooij
H H
HH
Wemer
J
J
Porsius
A J
AJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D004280:Dobutamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009203:Myocardial Infarction / Q000503:physiopathology*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D004280:Dobutamine; D008729:Methoxamine; D007545:Isoproterenol