Catecholamine antagonism of acetylcholine and dibutyrl guanosine 3',-5'-monophosphate in the mammalian ventricular myocardium

Abstract

After chemical sympathectomy we could demonstrate a negative inotropic effect of acetylcholine (ACh) on the cat ventricular myocardium as a direct catecholamine antagonism. Dose-response relationships for isoproterenol (IP) reveal a noncompetitive inhibition of the inotropic action of the catecholamine by ACh. A concentration of 10(-6) M ACh reduced the maximal IP-induced increase in tension by 58 +/- 13 percent (6-hydroxydopamine pretreatment) and by 65 +/- 10 percent (reserpine pretreatment); inhibition by endogenous ACh (released by field stimulation) was 36 +/- 10 percent and 38 +/- 8 percent, respectively. A concentration of 10(-3) M bibutyryl guanosine 3',5'-monophosphate (cAMP) produced a 17 +/- 7 percent reduction of the catecholamine-induced increase in tension (reserpine pretreatment). A cholinergic influence on the myocardial mechanics and metabolism of the heart may be relevant under stress situations. Vagal inhibition of the ventricular function is accentuated by an elevated sympathetic tone (Levy, 1971). If catecholamine-induced myocardial necrosis in addition to secondary effects of altered vessels are produced also by direct damage of the myocardial cell, then an influence of acetylcholine as a "natural" antagonist may be important.