Standen N B, Quayle J M, Davies N W, Brayden J E, Huang Y, Nelson M T
Department of Physiology, University of Leicester, United Kingdom.
Science. 1989 Jul 14;245(4914):177-80. doi: 10.1126/science.2501869.
Vasodilators are used clinically for the treatment of hypertension and heart failure. The effects of some vasodilators seem to be mediated by membrane hyperpolarization. The molecular basis of this hyperpolarization has been investigated by examining the properties of single K+ channels in arterial smooth muscle cells. The presence of adenosine triphosphate (ATP)-sensitive K+ channels in these cells was demonstrated at the single channel level. These channels were opened by the hyperpolarizing vasodilator cromakalim and inhibited by the ATP-sensitive K+ channel blocker glibenclamide. Furthermore, in arterial rings the vasorelaxing actions of the drugs diazoxide, cromakalim, and pinacidil and the hyperpolarizing actions of vasoactive intestinal polypeptide and acetylcholine were blocked by inhibitors of the ATP-sensitive K+ channels, suggesting that all these agents may act through a common pathway in smooth muscle by opening ATP-sensitive K+ channels.
血管扩张剂在临床上用于治疗高血压和心力衰竭。一些血管扩张剂的作用似乎是由膜超极化介导的。通过研究动脉平滑肌细胞中单个钾离子通道的特性，对这种超极化的分子基础进行了研究。在单通道水平上证实了这些细胞中存在三磷酸腺苷（ATP）敏感性钾离子通道。这些通道可被超极化血管扩张剂克罗卡林打开，并被ATP敏感性钾离子通道阻滞剂格列本脲抑制。此外，在动脉环中，药物二氮嗪、克罗卡林和匹那地尔的血管舒张作用以及血管活性肠肽和乙酰胆碱的超极化作用被ATP敏感性钾离子通道抑制剂阻断，这表明所有这些药物可能通过在平滑肌中打开ATP敏感性钾离子通道而通过共同途径发挥作用。
