State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Acta Pharmacol Sin. 2010 Jun;31(6):665-70. doi: 10.1038/aps.2010.40. Epub 2010 May 10.
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.
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.
MLB produced a concentration-dependent relaxation in mesenteric artery rings precontracted by norepinephrine (1 micromol/L) with an EC(50) of 111.3 micromol/L. MLB-induced relaxation was reduced in denuded artery rings with an EC(50) of 224.4 micromol/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 micromol/L) but inhibited K(V) currents (IC(50) 26.1 micromol/L) in a voltage- and concentration-dependent manner.
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.
研究 K(+) 通道和内皮细胞在丹参水溶性活性成分镁 lithospermate B (MLB)对血管作用中的作用。
采用离体大鼠肠系膜动脉环，观察 MLB 对 KCl 或去甲肾上腺素诱导收缩的影响。采用常规全细胞膜片钳技术，研究 MLB 对单个分离的肠系膜动脉心肌细胞 K(+)电流的影响。
MLB 对预先用去甲肾上腺素（1 μmol/L）收缩的肠系膜动脉环产生浓度依赖性松弛，EC（50）为 111.3 μmol/L。无内皮的动脉环中，MLB 诱导的松弛作用被减少，EC（50）为 224.4 μmol/L。MLB 在 N-硝基-L-精氨酸甲酯（L-NAME）存在下，可引起 KCl 预收缩的动脉环收缩，最大收缩值为 130.3%。在完整和无内皮的动脉环中，TEA 均可抑制 MLB 的血管舒张作用。在单个平滑肌细胞中，MLB 以电压和浓度依赖的方式激活 BK(Ca)电流（EC（50）为 156.3 μmol/L），但抑制 K(V)电流（IC（50）为 26.1 μmol/L）。
MLB 通过激活平滑肌细胞中的 BK(Ca)通道和增加内皮细胞释放 NO 来扩张血管，但在 L-NAME 存在下，它也可使 KCl 预收缩的动脉收缩。
