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 and 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. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 June 96