Mechanisms of vasorelaxation to gamma-mangostin in the rat aorta.

To investigate the effects of gamma-mangostin on vascular tone and its mechanisms in the isolated rat aorta. Aortic rings from male Wistar rats were precontracted with methoxamine. Changes in tension were measured using an isometric force transducer and recorded on the MacLab recording system. Vasorelaxant effects of gamma-mangostin were studied in the presence of 300 microM N(G)-nitro L-arginine methyl ester (L-NAME), 10 microM 1H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one (ODQ), 10 microM indomethacin, 60 mM KCl, 5 mM tetraethylammonium (TEA), 10 microM glibenclamide, 1 mM4-aminopyridine (4-AP) or 30 microM barium chloride (BaCl2). Moreover the effects of gamma-mangostin on contraction to CaCl2 were evaluated. Gamma-mangostin (1-100 microM) induced a concentration-dependent vasorelaxation in rat aortic rings precontracted with methoxamine. This effect was significantly reduced after removal of the endothelium and after pretreatment of the rings with L-NAME, ODQ, high KCl solution, or TEA. However, vasorelaxant responses to gamma-mangostin were not altered by indomethacin, 4-AP, BaCl2 or glibenclamide. Moreover, contractions to CaCl2 (10 mM-30 mM) were reduced by pre-treatment with gamma-mangostin (10 and 100 microM). Gamma-mangostin causes vasorelaxation which is mediated via the NO-cGMP pathway. Moreover activation of K+ channels and inhibition of extracellular Ca2+ influx from the extracellular space are largely involved in the relaxant effects of gamma-mangostin. These data suggest that gamma-mangostin may acts as an antihypertensive agent.