EFFECTS OF GINSENOSIDES ON VASODILATOR NERVE ACTIONS IN THE RAT PERFUSED MESENTERY ARE MEDIATED BY NITRIC-OXIDE

This study was designed to explore the effect of ginsenosides, saponin s from Panax ginseng, on the vasodilator nerve actions in the rat perf used mesentery and the mechanism of this effect. In the rat perfused m esentery, when adrenergic nerves were blocked by guanethidine (5 x 10( -6) M) and vascular muscle tone was increased with methoxamine (5 x 10 (-6)-10(-5) M), transmural field stimulation produced a frequency-depe ndent vasodilator response, which is due to the release of calcitonin gene-related peptide; ginsenosides significantly suppressed this vasod ilator response in a concentration-dependent manner (3-30 mu g mL(-1)) . After pretreatment with saponin (50 mu g mL(-1), 3 min) to damage de pendent manner (3-30 mu g mL(-1)). endothelial cells, this suppressing effect of ginsenosides was unaltered. However, the effect was abolish ed by N-omega-nitro-L-arginine methyl ester (L-NAME) (10-(4) M), an in hibitor of nitric oxide synthesis and addition of L-arginine (3 x 10(- 4) M) restored this suppressing effect. Methylene blue (10(-5) M), an inhibitor of guanylate cyclase, also abolished the suppressing effect of ginsenosides. However, ginsenosides did not alter the relaxation re sponses caused by exogenous calcitonin gene-related peptide administra tion. We conclude that ginsenosides can produce an inhibitory effect o n the vasodilator response prejunctionally in the rat perfused mesente ry and that this effect of ginsenosides may be mediated by nitric oxid e released from non-adrenergic, non-cholinergic nerves.