Inhibition by adenosine of catecholamine-induced increase in rat atrial contractility.
Because adenosine has been shown to attenuate the catecholamine-induced increase in myocardial cAMP formation and glycogen phosphorylase activity (Circ. Res. 43: 785-792, 1978), the present study was undertaken to determine whether the nucleoside inhibits the catecholamine-elicited increase in cardiac contractile state. Isolated rat atria were bathed in oxygenated physiologic saline and stimulated to contract isometrically at 2/s. Isoproterenol (0.1 microM) increased peak contractile force (PCF) by 96% and the rate of force development (+dF/dt) by 107%. Adenosine (10 microM) alone had no effect on these contractile parameters. Isoproterenol in the presence of adenosine increased PCF and +dF/dt only 15 and 14%, respectively. Elevation of bathing medium Ca2+ or administration of dibutyryl cAMP (DBcAMP) increased PCF and +dF/dt, but these responses were not decreased by adenosine. Inosine, adenine, adenosine 5'-monophosphate, and guanosine inhibited the isoproterenol-induced responses 5-22%. The results indicate that adenosine markedly inhibits, whereas some related purines only mildly attenuate, the catecholamine-elicited, but not the Ca2+- or DBcAMP-elicited, increases in contractility. Thus, adenosine may antagonize catecholamine-elicited glycogenolysis and enhanced contractile state in the heart by exerting an effect at the level of, or proximal to, cAMP formation.
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D016275:Atrial Function; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D004357:Drug Synergism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D013997:Time Factors
D003994:Bucladesine; D000241:Adenosine; D007545:Isoproterenol; D000109:Acetylcholine; D002118:Calcium