THE EFFECT OF TOLBUTAMIDE ON CONTRACTILITY AND CYCLIC ADENOSINE 3’: 5’-MONOPHOSPHATE CONCENTRATION IN THE INTACT BEATING RAT HEART1

ity and cyclic adenosine 3’:5’-monophosphate concentration in the intact beating rat heart. J. Pharmacol. Exp. Ther. 200: 166-173, 1977. The effect of tolbutamide on contractility and the concentration of cyclic adenosine 3’:5’-monophosphate (cyclic AMP) in ventricular muscle was examined in the intact beating rat heart. The hearts were perfused in a nonrecirculated (Langendorfi) fashion. Bolus injections of tolbutamide caused an increase in cardiac contractility. This increase in contracility was markedly inhibited when bovine albumin (3 g/100 ml) was present in the perfusing fluid. The increase in contractility caused by tolbuta-mide was not preceded by or associated with any change in the concentration of cyclic AMP in the ventricular muscle. Further studies utilizing a simultaneous injection of norepinephrine and tolbutamide demonstrated no significant effect of this combina-tion on the concentration of cardiac cyclic AMP produced by an injection of norepi-nephrine alone. Our findings suggest that in the intact beating rat heart the positive inotropic effect of tolbutamide is not mediated via an increase in the concentration of cardiac cyclic AMP and that tolbutamide does not significantly potentiate the effect o