Beta-Receptor Blockade and Myocardial Effects of Cardiac Glycosides

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Abstract
Because of suggestions that norepinephrine release from cardiac sympathetic nerves contributes to the myocardial action of digitalis, the effect of betareceptor blockade on these actions was determined. 10 -6 M propranolol did not alter the basal contractility of isolated kitten papillary muscles or of atrial strips from kittens, guinea pigs, rabbits, dogs, and chickens but decreased by 85% their inotropic response to norepinephrine released by tyramine or highintensity electrical stimulation. The same concentration of propranolol had no effect on cumulative inotropic concentration-effect curves for ouabain, acetylstrophanthidin, and digoxin in these preparations. Presence of propranolol did not modify the actions of cardiac glycosides on the time course of isometric contraction. Beta-receptor blockade was without effect on decreases in active tension and increases in resting tension induced by toxic concentrations of cardioactive steroids. The frequency of digitalis-induced automaticity in guinea pig atrial strips and kitten papillary muscles was significantly decreased by propranolol, presumably because of its direct electrophysiologic actions. Exposure of cat hearts to digoxin in vivo and to ouabain in vitro had no effect on myocardial norepinephrine concentrations. It is concluded that release of myocardial norepinephrine plays no role in the actions of cardiac glycosides on the heart.