Vasodilation of brain surface arterioles by blockade of Na–H+ antiport and its inhibition by inhibitors of KATP channel openers

Abstract Pial artrioles of rats were monitored in vivo and found to dilate in dose-dependent fashion upon application of either benzamil or ethyl isopropyl amiloride, both of which are inhibitors of the sodium–hydrogen antiport. Antiport blockade is known to decrease the internal pH of vascular smooth muscle (VSM). The dilation was blocked by 1 μm glibenclamide, which in that dose is a selective inhibitor of ATP sensitive potassium channels (K ATP ). The nitric oxide synthase inhibitor nitro- l arginine ( l -NNA) also blocked the response. Previous studies of this preparation under the same experimental conditions showed that l -NNA inhibited dilation by K ATP openers and that nitric oxide had no permissive action in this setting. Moreover, one study by others has demonstrated a pH sensitive site on the internal surface of K ATP while another study by others has demonstrated that sodium propionate, a direct acidifier of the cell, dilates rat basilar artery in K ATP -dependent fashion. Therefore, the present data support the following conclusions: Decrease of internal pH dilates brain arterioles; the response is K ATP dependent; in some situations, inhibitors of nitric oxide synthase can inhibit K ATP and K ATP -dependent dilations including those produced by decrease of internal pH.