[Cardiac effects of acetylcholine and its congeners].
Acetylcholine produced an elevation of the atrial pressure and decreased the systemic output dose-relatedly at 30 micrograms or more without producing any change in the heart rate. Negative chronotropic effects were observed only with doses of more than 600 micrograms. These effects of acetylcholine were enhanced by physostigmine and antagonized by atropine, while pindolol and 6-hydroxydopamine exerted no influence. Acetylcholine-induced elevation of atrial pressure and decrease of systemic output were similarly observed even when the heart was paced at a constant rate. Carbachol and methacholine produced qualitatively similar changes in the atrial pressure and systemic output. However, carbachol was unique in that it produced a dose-related negative chronotropic effect. Vagal stimulation induced an elevation of atrial pressure and a decrease of systemic output associated with bradycardia. Effects of vagal stimulation on atrial pressure and systemic output were abolished in the paced heart. These findings suggest that exogenous acetylcholine cannot reach the pacemaker site because of the abundant presence of cholinesterase in the region of the pacemaker, while acetylcholine released by vagal stimulation can reach the pacemaker site before being degraded by cholinesterase. The elevation of the atrial pressure and a decrease in the systemic output produced by exogenous acetylcholine can be ascribed to activation of the receptors in the ventricular myocardium, while the negative inotropic effects of vagal stimulation are due to an inhibition of atrial functions.
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology; D002302:Cardiac Output / Q000187:drug effects*; D002304:Cardiac Pacing, Artificial; D002802:Cholinesterases; D003864:Depression, Chemical; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology
D008688:Methacholine Compounds; D016210:Methacholine Chloride; D001285:Atropine; D002217:Carbachol; D010830:Physostigmine; D002802:Cholinesterases; D000109:Acetylcholine