Cardiac Effects of Clinically Available Kampo Medicine Assessed With Canine Isolated, Blood-Perfused Heart Preparations

Abstract

Cardiac effects of 10 kinds of clinically available Kampo medicines were investigated: Kakkon-to (TJ-1), Dai-saiko-to (TJ-8), Boi-ogi-to (TJ-20), Chorei-to (TJ-40), Rokumi-gan (TJ-87), Tsu-do-san (TJ-105), Gosha-jinki-gan (TJ-107), San'o-shashin-to (TJ-113), Sairei-to (TJ-114) and Inchin-gorei-san (TJ-117). Chronotropic and inotropic effects were studied using canine isolated, blood-perfused heart preparations, while subcellular mechanisms were analyzed by measuring the drug-induced changes of the adenylate cyclase activity in the canine ventricular membrane preparation. Intracoronary injections of TJ-1, TJ-20, TJ-105 and TJ-113 increased the sinoatrial rate and developed tension of papillary muscle in a dose-related manner, which was significantly attenuated by the pretreatment of the preparations with beta-blocker propranolol. Meanwhile, the other extracts hardly affected these parameters. TJ-1, TJ-20 and TJ-113 increased the adenylate cyclase activity in a dose-related manner, but their potency was significantly less compared with that by an equivalent concentration of isoproterenol. Moreover, TJ-105 did not increase the adenylate cyclase activity. These results suggest that the positive chronotropic and inotropic effects of TJ-1, TJ-20, TJ- 105 and TJ-113 may be exerted through the direct stimulation of the beta-adrenoceptor and/or the norepinephrine release from the postganglionic nerve terminals in the heart.