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

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.