Electropharmacological actions of Ginkgo biloba extract on vascular smooth and heart muscles

Abstract

Ginkgo biloba extract (GBE) is composed mostly of two constituents: One is terpenoids (such as bilobalide, ginkgolides A, B and C), and the other is flavonoids (such as quercetin and rutin). After oral administration of GBE (160 mg) to healthy volunteers, the plasma concentrations of ginkgolides A and B and bilobalide are 41.8, 5.6 and 37.6 ng/ml, respectively. GBE and bilobalide cause a potent concentration-dependent relaxation. N G-Monomethyl- l-arginine acetate ( l-NMMA), an NO synthesis inhibitor, reduces the vasodilation induced by GBE. Furthermore, the vasorelaxation of GBE is attenuated in Ca 2+-free medium. Bilobalide possesses similar mechanisms. The other constituents also produce vasorelaxation. On the other hand, all the compounds markedly modify the action potential configuration in guinea pig ventricular cardiomyocytes. GBE prolongs the action potential duration (APD), whereas bilobalide shortens the APD. In patch-clamp experiments, GBE markedly inhibits the Ca 2+ current ( I Ca), the delayed rectifier K + current ( I K) and the inwardly rectifying K + current ( I K1). On the contrary bilobalide enhances the I Ca and I K currents concentration-dependently. The other constituents do not cause their actions in a uniform direction. In the rat sino-atrial (SA) node, GBE causes a negative chronotropic effect. These results indicate that GBE and the constituents produce effective electropharmacological actions in the cardiomyocytes and cause vasodilation, mainly due to the inhibitions of Ca 2+ influx through the Ca 2+ channel and the activation of NO release in the endothelium and aortic vascular muscles.