Impaired beta-adrenergic stimulation in the uninvolved ventricle post-acute myocardial infarction: reversible defect due to excessive circulating catecholamine-induced decline in number and affinity of beta-receptors.
Left ventricular infarction (AMI) was produced in experimental animals and the contractile response to isoproterenol was tested in the isolated perfused heart preparation. Adenylate cyclase activity, phosphodiesterase activity, and beta-receptor binding characteristics were determined in a sarcolemmal preparation of the right ventricle of the same hearts. Three days post-AMI the dose-response curve for isoproterenol of right ventricular dP/dtmax was significantly depressed, while the inotropic effect of histamine was not impaired. Stimulation of adenylate cyclase activity by isoproterenol was reduced by 70% in the membrane preparation, whereas histamine and NaF stimulation rates were unaltered; phosphodiesterase activity was unchanged. In contrast, beta-receptor binding studies with [3H]-DHA1 indicated 74% loss and 10 times lowered affinity (KD) of the remaining beta-receptors, while specific [3H]-QNB1 binding was unchanged. All of the above alterations were prevented by pretreatment with reserpine or metoprolol. It is concluded that these abnormalities in the nonischemic surviving myocardium post-AMI are the result of specific reversible damage of sarcolemmal beta-receptors due to excessive levels of circulating catecholamines.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002395:Catecholamines / Q000097:blood*; D003326:Coronary Circulation; D005260:Female; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology; D008790:Metoprolol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000097:blood / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D012110:Reserpine / Q000494:pharmacology
D002395:Catecholamines; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D012110:Reserpine; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases; D008790:Metoprolol; D007545:Isoproterenol