Hyperpolarizing vasodilators activate ATP-sensitive K⁺ channels in arterial smooth muscle

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⁺ channel, suggesting that all these agents may act through a common pathway in smooth muscle by opening ATP-sensitive K⁺ channels.