Blockade of ATP-sensitive potassium channels in cerebral arterioles inhibits vasoconstriction from hypocapnic alkalosis in cats

Background and Purpose-Recent studies have shown that the cerebral arteriol ar 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 CO2 is a continuum, with hypercap nic acidosis causing vasodilation and hypocapnic alkalosis causing vasocons triction, it would be expected that the response to hypocapnic alkalosis wo uld 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 g lyburide- on the cerebral arteriolar constriction caused by graded hypocapn ia induced by hyperventilation in anesthetized cats equipped with cranial w indows. Results-Hypocapnic alkalosis caused dose-dependent vasoconstriction that wa s inhibited completely by each of the 3 inhibitors of K-ATP channels. The b lockade induced by these agents was eliminated in the presence of topical L -lysine (5 mu mol/L). Conclusions-The findings show that agents which inhibit ATP-sensitive potas sium channels in cerebral arterioles inhibit the vasoconstriction from hypo capnic alkalosis. These and earlier results showing that inhibition of K-AT P channels inhibited dilation from hypercapnic acidosis demonstrate that th e response to CO2 in cerebral arterioles is mediated by the opening and clo sing of K-ATP channels.