Mesaconitine-induced relaxation in rat aorta: involvement of Ca2+ influx and nitric-oxide synthase in the endothelium
| Autor: | Mana Mitamura, Syunji Horie, Masaru Sakaguchi, Kazuo Watanabe, Shizuko Tsuchiya, Akiyoshi Someya, Toshihiko Murayama, Johan Van de Voorde |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Atropine
Male Contraction (grammar) Thapsigargin Endothelium Aconitine chemistry.chemical_element Tetrodotoxin In Vitro Techniques Pharmacology Calcium Hexamethonium Calcium Chloride Phenylephrine chemistry.chemical_compound medicine.artery Extracellular medicine Animals Vasoconstrictor Agents Thoracic aorta Enzyme Inhibitors Rats Wistar Aorta Dose-Response Relationship Drug biology Rats Vasodilation Nitric oxide synthase NG-Nitroarginine Methyl Ester medicine.anatomical_structure Biochemistry chemistry Vasoconstriction biology.protein Endothelium Vascular Nitric Oxide Synthase Acetylcholine medicine.drug |
| Zdroj: | European Journal of Pharmacology. 436:217-225 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/s0014-2999(01)01623-5 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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