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(Stroke. 1998;29:817-823.)
© 1998 American Heart Association, Inc.

Original Contributions

Antioxidants Inhibit ATP-Sensitive Potassium Channels in Cerebral Arterioles

Enoch P. Wei, PhD; Hermes A. Kontos, MD, PhD; Joseph S. Beckman, PhD

From the Department of Medicine, Medical College of Virginia Campus of Virginia Commonwealth University, Richmond (E.P.W., H.A.K.), and Department of Anesthesiology, University of Alabama at Birmingham (J.S.B.).

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

Background and Purpose—Hydrogen peroxide and peroxynitrite are capable of generating hydroxyl radical and are commonly suspected as sources of this radical in tissues. It would be useful to distinguish the source of hydroxyl radical in pathophysiological conditions and to clarify the mechanisms by which antioxidants modify vascular actions of oxidants.

Methods—We investigated the effect of three antioxidants—dimethylsulfoxide (DMSO), salicylate, and L-cysteine—on the cerebral arteriolar dilation caused by topical application of hydrogen peroxide and peroxynitrite in anesthetized cats equipped with cranial windows. We also tested the effect of these antioxidants on the vasodilation caused by pinacidil and cromakalim, two known openers of ATP-sensitive potassium channels.

Results—DMSO was more effective in inhibiting dilation from hydrogen peroxide, whereas salicylate and L-cysteine were more effective in inhibiting dilation from peroxynitrite. All three antioxidants inhibited dilation in concentrations that were remarkably low (<1 mmol/L). All three antioxidants inhibited vasodilation from two known potassium channel openers, pinacidil and cromakalim. Their effect was specific because they did not affect dilation from adenosine or nitroprusside.

Conclusions—The findings show that antioxidants block ATP-sensitive potassium channels in cerebral arterioles. This appears to be the mechanism by which antioxidants inhibit the dilation from hydrogen peroxide and peroxynitrite and not through scavenging of a common intermediate, ie, hydroxyl radical. The differences between effectiveness in inhibiting dilation from hydrogen peroxide and peroxynitrite by various antioxidants suggest that hydrogen peroxide and peroxynitrite act at two different sites, one in a water-soluble environment and the other in a lipid-soluble environment.

Editorial Comment

Frank M. Faraci, PhD, Guest Editor

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

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