Cerebral vasodilation during hypercapnia. Role of glibenclamide-sensitive potassium channels and nitric oxide.

Abstract

The purpose of these experiments was to examine mechanisms by which hypercapnia produces vasodilatation in brain. We examined the hypothesis that dilatation of cerebral arterioles during hypercapnia is dependent on activation of ATP-sensitive potassium channels and formation of nitric oxide. Diameters of cerebral arterioles were measured using a closed cranial window in anesthetized rabbits. Changes in diameter of arterioles were measured in response to topical application of acetylcholine and sodium nitroprusside and during two levels of systemic hypercapnia. Increasing arterial PCO2 from 32 +/- 1 mm Hg (mean +/- SE) to 54 +/- 1 and 66 +/- 1 mm Hg dilated cerebral arterioles by 25 +/- 3% and 38 +/- 5%, respectively, from a control diameter of 93 +/- 3 microns. The response to the low level of hypercapnia was attenuated (25 +/- 3% versus 16 +/- 4%, P < .05) by glibenclamide (1 mumol/L), an inhibitor of ATP-sensitive potassium channels. Vasodilatation in response to the high level of hypercapnia was not affected by glibenclamide. Increases in arteriolar diameter in response to sodium nitroprusside were not inhibited by glibenclamide. NG-nitro-L-arginine (300 mumol/L), an inhibitor of nitric oxide synthase, completely inhibited dilatation of cerebral arterioles in response to the low level of hypercapnia and inhibited vasodilatation during the high level of hypercapnia by 66%. Thus, activation of glibenclamide-sensitive potassium channels may contribute to dilatation of cerebral arterioles during hypercapnia. Cerebral vasodilatation during hypercapnia is dependent in large part on production of nitric oxide.