Cardiac Actions of Glucagon

Abstract

Glucagon increased heart rate and contractile force in the anesthetized dog and increased isometric tension in the isolated dog papillary muscle. The positive inotropic and chronotropic responses were not abolished or reduced by previous administration of the beta-receptor blocking agent propranolol, in doses of 0.5 mg/kg. Glucagon increased the force and rate of cardiac contraction even when cardiac-depressant doses of propranolol, 2 mg/kg, had been given. Previous treatment with reserpine (1.0 mg/kg on each of 3 consecutive days) failed to diminish the positive inotropic and chronotropic effects of glucagon. However, previous administration of tyramine, 0.05 mg/kg, which resulted in a positive inotropic response in the dog, significantly reduced the glucagon-induced positive inotropic response. Theophylline, 10 mg/kg, likewise prevented the inotropic action of glucagon without preventing the positive inotropic effect of calcium chloride. The increase in isometric tension produced by glucagon in the isolated dog papillary muscle was prevented during simultaneous exposure of the muscles to acetylcholine. The results of these studies are discussed in reference to the known metabolic actions of glucagon and the catecholamines and the possibility that they both share a common mechanism of action mediated through an increase in the intracellular concentration of cyclic 3',5' AMP.