CARDIAC EFFECTS OF ACETYLCHOLINE IN RAT HEARTS - ROLE OF ENDOTHELIUM-DERIVED RELAXING FACTOR AND PROSTAGLANDINS

We examined the effects of acetylcholine (ACh) on coronary perfusion p ressure (CPP) and force of cardiac contraction (FCC) in isolated rat h earts. Perfusion of hearts with ACh increased both CPP and the FCC, wh ereas cardiac contraction rate fell. These effects of ACh were abolish ed by atropine but were not affected by the beta1-adrenergic antagonis t metoprolol. The nonselective beta-adrenergic antagonist propranolol decreased ACh-mediated increase in FCC but did not affect the rise in CPP. Pretreatment of hearts with cyclooxygenase inhibitor indomethacin or thromboxane (Tx) A2-endoperoxide receptor antagonist SQ 29,548 dec reased ACh-mediated increase in CPP and FCC, suggesting release of TxA 2 in the microvasculature, which may partially account for the increas e in CPP and FCC with ACh infusion. In contrast to the effect of indom ethacin and SQ 29,548, pretreatment of hearts with endothelium-derived relaxing factor (EDRF) synthetase inhibitor N(G)-monomethyl-L-arginin e (L-NMMA) or guanylate cyclase inhibitor methylene blue potentiated A Ch-mediated increase in CPP and attenuated the increase in FCC, sugges ting that ACh-mediated increase in CPP is modified by basal EDRF relea se. Thus the cardiac effects of ACh are related to muscarinic receptor activation, and the release of prostaglandins and EDRF modulates the effects of ACh in isolated rat heart.