Magnesium lithospermate B dilates mesenteric arteries by activating BKCa currents and contracts arteries by inhibiting K-V currents

Aim: To examine the involvement of K+ channels and endothelium in the vascular effects of magnesium lithospermate B (MLB), a hydrophilic active component of Salviae miltiorrhiza Radix. Methods: Isolated rat mesenteric artery rings were employed to investigate the effects of MLB on KCl- or norepinephrine-induced contractions. Conventional whole-cell patch-clamp technique was used to study the effects of MLB on K+ currents in single isolated mesenteric artery myocytes. Results: MLB produced a concentration-dependent relaxation in mesenteric artery rings precontracted by norepinephrine (1 mu mol/L) with an EC50 of 111.3 mu mol/L. MLB-induced relaxation was reduced in denuded artery rings with an EC50 of 224.4 mu mol/L. MLB caused contractions in KCl-precontracted artery rings in the presence of N-nitro-L-arginine methyl ester (L-NAME) with a maximal value of 130.3%. The vasodilatory effect of MLB was inhibited by tetraethylammonium (TEA) in both intact and denuded artery rings. In single smooth muscle cells, MLB activated BKCa currents (EC50 156.3 mu mol/L) but inhibited K-V currents (IC50 26.1 mu mol/L) in a voltage- and concentration-dependent manner. Conclusion: MLB dilated arteries by activating BKCa channels in smooth muscle cells and increasing NO release from endothelium, but it also contracted arteries precontracted with KCl in the presence of L-NAME.