OxyFile #413

Mechanisms of cerebral vasodilation by superoxide hydrogen 
peroxide and peroxynitrite. 

Wei, Enoch P., Hermes A. Kontos, Joseph S. Beckman. 
Department of Medicine, Medical College of Virginia, Virginia 
Commonwealth University, 
Richmond, Virginia 23298 
Department of Anesthesiology, 
University of Alabama at Birmingham, 
Birmingham, Alabama 35233 

APStracts 3:0253H, 1996.

We investigated the role of potassium channels in the vasodilator 
action of hydrogen peroxide, peroxynitrite and superoxide on 
cerebral arterioles. We studied the effect of topical application 
of these agents in anesthetized cats equipped with cranial 
windows. Hydrogen peroxide and peroxynitrite induced dose-
dependent dilation which was inhibited by glyburide, an inhibitor 
of ATP-sensitive potassium channels. Superoxide, generated by 
xanthine oxidase acting on xanthine in the presence of catalase, 
also induced dose-dependent dilation of cerebral arterioles, which 
was unaffected by glyburide, but inhibited completely by 
tetraethylammonium chloride, an inhibitor of calcium-activated 
potassium channels. The vasodilations from hydrogen peroxide, 
peroxynitrite, or superoxide were unaffected by inhibition of 
soluble guanylate cyclase with LY83583. The findings provide 
pharmacological evidence that hydrogen peroxide and peroxynitrite 
reversibly dilate cerebral arterioles by activating ATP-sensitive 
potassium channels, probably through an oxidant mechanism, while 
superoxide dilates cerebral arterioles by opening calcium-
activated potassium channels. Activation of soluble guanylate 
cyclase is not a mediator of the vasodilator action of these 
agents in cerebral arterioles. 

Received 4 March 1996; accepted in final form 4 June 1996.
APS Manuscript Number H213-6.
Article publication pending Am. J. Physiol. (Heart Circ. 
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 June 96