Magnesium lithospermate B dilates mesenteric arteries by activating BK Ca 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 μmol/L) with an EC 50 of 111.3 μmol/L. MLB-induced relaxation was reduced in denuded artery rings with an EC 50 of 224.4 μmol/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 BK Ca currents (EC 50 156.3 μmol/L) but inhibited K V currents (IC 50 26.1 μmol/L) in a voltage- and concentration-dependent manner. Conclusion: MLB dilated arteries by activating BK Ca 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.