INTERACTIONS OF ACETYLCHOLINE AND EPINEPHRINE ON CONTRACTILITY, GLYCOGEN AND PHOSPHORYLASE ACTIVITY OF ISOLATED MAMMALIAN HEARTS

¹ Department of Pharmacology, Woman's Medical College of Pennsylvania, Philadelphia, Pennsylvania

Isolated, perfused hearts with ventricular rate controlled electrically were infused for one hour with epinephrine (EPI) and acetylcholine (ACh), singly and in combination. Previously it was found that ACh inhibits the glycogenolytic effect of EPI on atria and ventricles of isolated guinea-pig hearts in concentrations which do not antagonize the positive inotropic effect of EPI. In the present study in guinea-pig, rabbit and cat hearts, ACh alone had no effect on ventricular contractile force. EPI produced positive inotropic effects which were not altered by the presence of ACh. However, the glycogenolytic effect of EPI on the hearts was markedly inhibited by ACh. Phosphorylase activity and contractile force were determined in guinea-pig hearts into which drugs were infused for periods of time up to one hour. The positive inotropic effect and the activation of phosphorylase produced by EPI were maintained throughout the one-hour infusion. ACh did not modify the positive inotropic effect of EPI, but ACh significantly antagonized the activation of phosphorylase by EPI after one minute of exposure to both agents and progressively reduced the effect of EPI to almost complete inhibition at the end of one hour. These results indicate a clear dissociation between the positive inotropic action of epinephrine and its activation of phosphorylase.