Apamin/charybdotoxin-sensitive endothelial K+ channels contribute to acetylcholine-induced, NO-dependent vasorelaxation of rat aorta.

BACKGROUND: Activation of endothelial K+ channels and the subsequent increase in intracellular Ca2+, may be an important step in the release of relaxant factors in response to endothelium-dependent vasodilator agents. However, the type of K+ channel involved in hyperpolarization of the endothelium and the subsequent release of relaxing factors remains to be defined. MATERIAL AND METHODS: Rat aortic rings precontracted with U46619 were used to address the effects of inhibitors of K+ channels on the vasorelaxant response to acetylcholine (Ach). As responses to Ach were mediated solely by endothelium-derived NO and responses to NO derived from nitroprusside were unaffected by inhibition K+ channels, any effect of K+ channel inhibitors could be attributed to actions on endothelial K+ channels to modify NO release. RESULTS: Tetraethylammonium (TEA) and elevated K+ attenuated the relaxant effect of Ach, indicating a role for K+ channels in NO release. The Ca2+-activated K+ channel inhibitors, apamin, charybdotoxin and iberiotoxin as well as glibenclamide and BaCl2, inhibitors of ATP-sensitive K+ channels and inwardly rectifying K+ channels, respectively, did not affect the response to Ach. However, a combination of apamin and charybdotoxin, but not apamin and iberiotoxin, attenuated the vasorelaxant response to Ach. CONCLUSIONS: The results of this study indicate that NO release in response to Ach involves activation of an endothelial K+ channel that is inhibited by a combination of apamin and charybdotoxin.