EFFECT OF TOLBUTAMIDE ON CONTRACTILITY AND CYCLIC ADENOSINE 3'=5'-MONOPHOSPHATE CONCENTRATION IN INTACT BEATING RAT-HEART

  • 1 January 1977
    • journal article
    • research article
    • Vol. 200  (1) , 166-173
Abstract
The effect of tolbutamide on contractility and the concentration of cyclic[c]AMP in ventricular muscle was examined in the intact beating rat heart. The hearts were perfused in a nonrecirculated (Langendorff) fashion. Bolus injections of tolbutamide caused an increase in cardiac contractility. This increase in contractility was markedly inhibited when bovine albumin (3 g/100 ml) was present in the perfusing fluid. The increase in contractility caused by tolbutamide was not preceded by or associated with any change in the ventricular muscle cAMP concentration. Further studies utilizing a simultaneous injection of norepinephrine and tolbutamide demonstrated no significant effect of this combination on the concentration of cardiac cAMP produced by an injection of norepinephrine alone. In the intact beating rat heart the positive inotropic effect of tolbutamide is not mediated via an increase in the concentration of cardiac cAMP; tolbutamide probably does not significantly potentiate the effect of catecholamines on cardiac cAMP concentration. [The long-term clinical study of the University Group Diabetes Program (1970) suggested that there is an increased incidence of cardiovascular deaths in adult onset diabetic patients taking tolbutamide.].