Blockade of ATP-Sensitive Potassium Channels in Cerebral Arterioles Inhibits Vasoconstriction From Hypocapnic Alkalosis in Cats

Abstract

Background and Purpose —Recent studies have shown that the cerebral arteriolar dilation from hypercapnic acidosis is blocked by agents which inhibit K ATP channels. These findings suggested that this response is due to opening of K ATP channels. Because the repose to CO 2 is a continuum, with hypercapnic acidosis causing vasodilation and hypocapnic alkalosis causing vasoconstriction, it would be expected that the response to hypocapnic alkalosis would be due to closing of K ATP channels. There are no studies of the effect of inhibition of K ATP channels on the response to hypocapnic alkalosis. Methods —We investigated the effect of 3 agents that in earlier studies were found to inhibit K ATP channels— N G -nitro- l -arginine, hydroxylysine, and glyburide—on the cerebral arteriolar constriction caused by graded hypocapnia induced by hyperventilation in anesthetized cats equipped with cranial windows. Results —Hypocapnic alkalosis caused dose-dependent vasoconstriction that was inhibited completely by each of the 3 inhibitors of K ATP channels. The blockade induced by these agents was eliminated in the presence of topical l -lysine (5 μmol/L). Conclusions —The findings show that agents which inhibit ATP-sensitive potassium channels in cerebral arterioles inhibit the vasoconstriction from hypocapnic alkalosis. These and earlier results showing that inhibition of K ATP channels inhibited dilation from hypercapnic acidosis demonstrate that the response to CO 2 in cerebral arterioles is mediated by the opening and closing of K ATP channels.