EFFECT OF NITRIC-OXIDE AND POTASSIUM CHANNEL AGONISTS AND INHIBITORS ON BASILAR ARTERY DIAMETER

The first goal of this study was to examine the hypothesis that dilata tion of the basilar artery in response to activation of ATP-sensitive K+ channels is mediated by nitric oxide (NO). Diameter of the basilar artery (209 +/- 5 mu m, mean +/- SE) was measured using a cranial wind ow in anesthetized rats. Aprikalim (a direct activator of ATP-sensitiv e K+ channels) dilated the basilar artery under control conditions. In hibition of endogenous NO production with N-G-nitro-L-arginine (L-NNA, 10(-4) M) did not alter responses to aprikalim. The second goal was t o determine whether vasodilatation in response to NO is dependent on a ctivation of calcium-activated K+ channels. Tetraethylammonium (TEA, 1 0(-3) M), an inhibitor of calcium-activated K+ channels, did not affec t dilator responses to sodium nitroprusside (an NO donor) under contro l conditions. Responses to nitroprusside (10(-8) and 10(-7) M) mere au gmented more than twofold during application of L-NNA. In the presence of L-NNA, the augmented portion of the response to nitroprusside was inhibited by TEA and iberiotoxin (5 x 10(-8) M, a highly selective inh ibitor of calcium-activated K+ channels), but it was not inhibited by glibenclamide (10(-6) M), an inhibitor of ATP-sensitive K+ channels. T hese findings suggest that dilator responses of the basilar artery to an activator of ATP-sensitive potassium channels are not mediated by N O. Calcium-activated K+ channels may not normally contribute to dilato r responses of the basilar artery to nitroprusside. The effects of TEA and iberiotoxin suggest that when endogenous production of NO is inhi bited, sodium nitroprusside causes the opening of calcium-activated K channels, contributing to an augmented vasodilator response.