STUDIES ON THE RELATIONSHIP BETWEEN PHOSPHORYLASE ACTIVATION AND INCREASE IN CARDIAC FUNCTION

¹ Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

The relation among changes in heart rate, isometric contractile force and phosphorylase a activity was investigated in the isolated rat heart perfused with Tyrode's solution. A good correlation between the increase in contractile force and phosphorylase a activity over a wide range of norepinephrine doses was observed. The interaction of norepinephrine and pronethalol revealed that the positive chronotropic effect and phosphorylase activation by norepinephrine were more sensitive to the blockade by pronethalol than was the positive inotropic action. Perfusion of the heart with Tyrode's solution at temperatures from 20-35°C produced no change in either contractile amplitude or phosphorylase a activity but did result in a marked increase in heart rate. Sudden increase in resting tension from 1 to 3 g increased contractile force without any change in heart rate or phosphorylase a activity. The results indicate that the activation of heart phosphorylase is not obligatory to increase in cardiac function, at least within certain limits.