VENTRICULAR CHOLINERGIC RECEPTOR SYSTEMS: INTERACTION WITH ADRENERGIC SYSTEMS

¹ National Heart Institute, Bethesda, Maryland

It has been demonstrated in several cardiac preparations that acetylcholine (ACh) may exert various effects upon the chronotropic and inotropic state of ventricular myocardium. In high doses ACh will cause a catecholamine-mediated positive inotropic response, but it will also antagonize other catecholamine-mediated metabolic effects on heart preparations. Mechanisms underlying the various cardiac effects of ACh were examined in isolated cat hearts (20 normal; 14 catecholamine depleted) perfused with a modified Krebs' solution and electrically paced. Maximum pressure developed in the isovolumically beating left ventricle was used as an index of contractility. In normal hearts ACh depressed contractility in doses of 10^-6 g to 10^-5 g; higher doses produced a positive inotropic effect which could be blocked by dl-propranolol or d-tubocurarine. A positive inotropic dose of ACh given prior to an equipotent dose of norepinephrine blocked the inotropic response to norepinephrine for 3 to 4 min. The administration of atropine to normal hearts shifted the dose-response curve for the ACh-mediated positive inotropic response to the left, and prevented inhibition of the response to norepinephrine by ACh. In catecholamine-depleted hearts only the negative inotropic effect of ACh was seen. However, the administration of ACh prior to norepinephrine still inhibited the norepinephrine response. These observations: 1) confirm previous reports of an ACh-norepinephrine antagonism on ventricular muscle; 2) indicate that the "nicotinic" action of ACh is not involved in this antagonism; and 3) demonstrate the time sequence and des-dependent nature of this phenomenon.