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.