Ginkgo biloba extract (GBE) is composed of mostly two constituents; one is terpenoids (such as bilobalide, ginkgolide A, B and C), and another is flavonoids (such as quercetin and rutin). All the compounds cause marked actions on the action potential configuaration in guinea pig ventricular cardiomyocytes. GBE prolongs the action potential duration (APD), whereas bilobalide shortens the APD. The Vmax decreases. The resting potential is unaffected. In voltage-clamp experiments, GBE markedly inhibits the Ca2+ current (ICa), the delayed rectifier K+ current (IK1). On the other hand, bilobalide enhances the ICa and the IK currents concentration-dependently. The other constituents are also not uniform at all. In rat sino-atrial (SA) node, GBE causes a negative chronotropic effect. The responses are almost reversible after a 10- to 20-min washout.
In addition, GBE causes a potent concentration-dependent relaxation. Bilobalide also causes the vasodilation. Ginkgolides A, B and C also dilate to the almost same extent. NG-monomethyl-L-arginine acetate (L-NMMA), a NO synthesis (NOS) inhibitor, reduces the vasodilation induced by GBE. Tetraethylammonium (TEA), a Ca2+ -activated K+ channel inhibitor, also decreases the GBE-induced relaxation, but not significantly. Indomethacin tends to reduce the GBE-induced vasorelaxation. Furthermore, the vasorelaxation of GBE is strongly attenuated in Ca2+ -free medium. Bilobalide possesses the similar vasorelaxation mechanisms. Flavonoids (quercetin and rutin) also produce the vasorelaxation.
These results indicate that even at acute administrations, GBE and the constituents produce the effective actions on the APD and the underlying ionic currents in cardiomyocytes, although each constituent does not exhibit a uniform response. Also, the results suggest that GBE causes the vasodilation, mainly due to the inhibitions of Ca2+ influx through Ca2+ channel and the activation of NO releasing in the endothelium and aortic vascular muscles.
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