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Friday 16 April 2004

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

By: Rosenblum WI, Wei EP, Kontos HA.

Brain Res 2004 Apr 16;1005(1-2):77-83

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 microm 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.

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