title: Ginkgo biloba extract-induced relaxation of rat aorta is associated with increase in endothelial intracellular calcium level.
abstract: Ginkgo biloba extract (GBE) has been used clinically for improving peripheral vascular diseases in France and Germany. In the present study, to clarify the pharmacological properties of vasodilation produced by GBE, we examined the effect of GBE and quercetin, one of the ingredients in GBE, on the thoracic aorta isolated from Wistar rats. GBE produced a dose-dependent relaxation in the aortic ring precontracted with noradrenaline, and the relaxation was abolished by L-N(G)-nitro arginine methyl ester (L-NAME). Quercetin produced a similar relaxation, which was also abolished by L-NAME. We then examined the effects of GBE and quercetin on the intracellular calcium level ([Ca2+]i) of cultured aortic endothelial cells using a fluorescent confocal microscopic imaging system. Both GBE and quercetin produced significant increases in [Ca2+]i in the endothelial cells. The increase in [Ca2+]i by quercetin (10(-6) M) was abolished by removing the extracellular Ca2+, but was not affected by thapsigargin, a calcium pump inhibitor. These findings suggest that a principal ingredient of GBE producing vasodilation is quercetin, which can activate nitric oxide synthesis and release by increasing [Ca2+]i in vascular endothelial cells.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kubota
authors.forename: N
authors.initials: N
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Umegaki
authors.forename: H
authors.initials: H
authors.lastname: Takenaka
authors.forename: H
authors.initials: H
authors.lastname: Mizuno
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Shinozuka
authors.forename: M
authors.initials: M
authors.lastname: Kunitomo
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005453:Fluorescence; D020441:Ginkgo biloba; D066298:In Vitro Techniques; D008297:Male; D018613:Microscopy, Confocal; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology; D051381:Rats; D019284:Thapsigargin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*; D000096983:Ginkgo Extract
chemical_list: D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D010936:Plant Extracts; D011794:Quercetin; D019284:Thapsigargin; D014665:Vasodilator Agents; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract