Acetylcholine-induced positive inotropy mediated by prostaglandin releasedfrom endocardial endothelium in mouse left atrium

The possible involvement of the endocardial endothelium in the positive ino tropic response of the mouse left atrium to acetylcholine was examined phar macologically. In mouse left atria, acetylcholine produced a biphasic inotr opic response: a transient decrease in contractile force followed by a late increase. The positive response was not affected by the presence of phento lamine and propranolol. but was almost abolished by pretreatment of the pre paration with 1% Triton X-100, which denudes the endocardium of its endothe lium. Nordihydroguaiaeretic acid, N-G-nitro-L-arginine, BQ-123 and BQ-788 h ad no effect on the inotropic responses to acetylcholine, but indomethacin completely abolished the positive response. Prostaglandins and their analog ues had a positive inotropic effect with a potency order PGF(2 alpha)> PGD > PGE(2)> U46619. whereas beraprost had no effect. Neither Triton X-100 pre treatment nor the presence of indomethacin affected the positive inotropic effect of PGF(2 alpha). Acetylcholine and PGF(2 alpha) prolonged the action potential duration similarly. These results suggest that the acetylcholine -induced positive inotropic response in mouse left atria is mediated by pro staglandin released from the endocardial endothelium.