title: Mesaconitine-induced relaxation in rat aorta: involvement of Ca2+ influx and nitric-oxide synthase in the endothelium.
abstract: Aconiti tuber, roots of aconite (Aconitum japonicum), is an oriental herbal medicine used for centuries in Japan and China to improve the health of persons with a weak constitution and poor metabolism. We investigated the effects of mesaconitine, one of the aconite alkaloids in Aconiti tuber, on the contraction and free intracellular Ca2+ concentration ([Ca2+]i) level in isolated rat thoracic aorta. Mesaconitine at 30 microM inhibited 3 microM phenylephrine-induced contraction in the endothelium-intact, but not endothelium-denuded, aortic rings. The effect of mesaconitine was dependent on external Ca2+ concentrations. The relaxation induced by mesaconitine was abolished by N(omega)-nitro-L-arginine methyl ester (0.1 mM, an inhibitor of nitric-oxide synthase), as well as the relaxation induced by acetylcholine. Acetylcholine induced relaxation in two phases in our conditions; the initial phase was transient and external Ca2+ -independent, and the second phase was sustained and external Ca2+ -dependent. Treatment with 100 nM thapsigargin, which depleted intracellular Ca2+ stores, inhibited acetylcholine-induced, but not mesaconitine-induced, relaxation. Mesaconitine increased the [Ca2+]i level in endothelial cells by influx of Ca2+ from extracellular spaces. These findings suggest that mesaconitine-induced Ca2+ influx and activation of nitric-oxide synthase in endothelial cells and, thus, induced vasorelaxation in rat aorta.
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522, Japan.
authors.forename: Mana
authors.initials: M
authors.lastname: Mitamura
authors.forename: Syunji
authors.initials: S
authors.lastname: Horie
authors.forename: Masaru
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Someya
authors.forename: Shizuko
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: Johan
authors.initials: J
authors.lastname: Van de Voorde
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Murayama
authors.forename: Kazuo
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002122:Calcium Chloride / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D018738:Hexamethonium; D013779:Tetrodotoxin; C019470:mesaconitine; D019284:Thapsigargin; D001285:Atropine; D019001:Nitric Oxide Synthase; D002122:Calcium Chloride; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D000157:Aconitine