Biphasic Action of Acetylcholine on Ventricular Myocardium

Abstract

Intracoronary infusions of acetylcholine have demonstrated two actions of this neurohumoral agent on ventricular myocardium: 1) an antagonism to the more forceful contractions evoked by adrenergic stimuli (sympathomimetic drugs or stellate stimulation), and 2) a sympathomimetic or positive inotropic effect (? release of a positive inotropic substance from the myocardium). The increased contractility ("rebound") was observed only after the infusion of acetylcholine was stopped; in the presence of physostigmine the "rebound" was absent. Atropine blocked both the cardio-inhibitory and cardio-excitatory actions of acetylcholine. Failure of hexamethonium and bretylium to block the "rebound" suggests that acetylcholine acts at a peripheral site. The possible catecholamine nature of the agent could not be established by direct analysis of coronary venous blood, by the use of an adrenergic beta receptor blocking agent or by pretreatment of the animals with reserpine; neither drug blocked the "rebound."