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(Stroke. 1999;30:851-854.)
© 1999 American Heart Association, Inc.

Original Contributions

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

Enoch P. Wei, PhD Hermes A. Kontos, MD, PhD

From the Department of Medicine, Medical College of Virginia Campus of Virginia Commonwealth University, Richmond, Va.

Correspondence to Hermes A. Kontos, MD, PhD, Medical College of Virginia Campus, Virginia Commonwealth University, PO Box 980549, Richmond, VA 23298-0549. E-mail hakontos{at}vcu.edu

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 CO₂ 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 CO₂ in cerebral arterioles is mediated by the opening and closing of K_ATP channels.

Editorial Comment

Frank M. Faraci, PhD, Guest Editor

Department of Internal Medicine, Cardiovascular Center, University of Iowa College of Medicine, Iowa City, Iowa

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