Mechanisms for the vasodilations induced by Ginkgo biloba extract and its main constituent, bilobalide, in rat aorta.
Vasodilating actions of Ginkgo biloba extract (GBE) and bilobalide, a main constituent, were examined using rat aorta ring strips. GBE at the concentration ranges from 0.03 to 3 mg/ml had a potent concentration-dependent relaxation, reaching 70 +/- 4.5% (n = 6, P < 0.001) at 3 mg/ml. Bilobalide at 0.1 to 100 microM also caused the relaxation in a concentration-dependent manner. At 100 microM, bilobalide caused dilation by 17.6 +/- 3.9% (n = 7, P < 0.05). NG-monomethyl-L-arginine acetate (L-NMMA)(100 microM), an NO synthesis inhibitor, reduced the vasodilation of GBE (3 mg/ml) to 57.6 +/- 2.5% (n = 6, P < 0.05), and was accompanied with a decrease in the rate of relaxation. Tetraethylammonium (TEA)(100 microM), a Ca(2+)-activated K(+) channel inhibitor, also decreased the GBE (3 mg/ml)-induced relaxation to 63.1 +/- 4.6% (n = 6), but not significantly. Indomethacin tended to reduce the GBE (3 mg/ml)-induced vasorelaxation to 67.3 +/- 4.1% (n = 6). In contrast, the vasorelaxation of GBE (3 mg/ml) was strongly attenuated to 53 +/- 6.1% (n = 7, P < 0.05) in Ca(2+)-free medium. Similarly, the vasorelaxation induced by bilobalide significantly decreased both by pretreatment with NO inhibitor (L-NMMA) and in Ca(2+)-free solution. These results indicate that the relaxation induced by GBE would be due to the inhibition of Ca(2+) influx through the Ca(2+) channel and the activation of NO release, and might be in part due to the inhibitions of Ca(2+)-activated K(+) current and PGI(2) release, in the endothelium and aortic vascular muscles. Bilobalide possesses the similar mechanisms for the vasodilation.
Nishida
Seiichiro
S
Department of Pharmacology, Division of Crude and Herbal Medicine, Nara Medical University, Kashihara, Nara 634-8521, Japan.
Satoh
Hiroyasu
H
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D003517:Cyclopentanes / Q000494:pharmacology*; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000187:drug effects; D005663:Furans / Q000494:pharmacology*; D020441:Ginkgo biloba / Q000737:chemistry*; D046934:Ginkgolides; D007213:Indomethacin / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D003517:Cyclopentanes; D004224:Diterpenes; D004338:Drug Combinations; D005663:Furans; D046934:Ginkgolides; D010936:Plant Extracts; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D019789:Tetraethylammonium; C073710:bilobalide; D002118:Calcium; D007213:Indomethacin