NO-mediated, endothelium-dependent vasorelaxation by aconite alkaloid mesaconitine

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 effects of mesaconitine, one of the alkaloids in aconite, on the contraction in rat isolated thoracic aorta. Mesaconitine inhibited phenylephrine-induced contraction in the endothelium-intact, but not endothelium-denuded, aortic rings. The effect of mesaconitine was dependent on external CaCl2 concentration. The mesaconitine-induced relaxation was abolished by N square-nitro-L-arginine methyl ester (an inhibitor of nitric-oxide synthase), as well as the acetylcholine-induced relaxation. Mesaconitine increased the free intracellular Ca2+ level in endothelium by the influx of Ca2+ from extracellular spaces. These results suggest that mesaconitine elicits Ca2+ influx and activation of nitric-oxide synthase in endothelium, resulting in vasorelaxation in rat aorta.