MECHANISMS OF CEREBRAL VASODILATION BY SUPEROXIDE, HYDROGEN-PEROXIDE,AND PEROXYNITRITE

We investigated the role of potassium channels in the vasodilator acti on of hydrogen peroxide, peroxynitrite, and superoxide on cerebral art erioles. 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 that was inhibited b y glyburide, an inhibitor of ATP-sensitive potassium channels. Superox ide, generated by xanthine oxidase acting an xanthine in the presence of catalase, also induced dose-dependent dilation of cerebral arteriol es that was unaffected by glyburide but inhibited completely by tetrae thylammonium chloride, an inhibitor of calcium-activated potassium cha nnels. The vasodilations from hydrogen peroxide, peroxynitrite, or sup eroxide were unaffected by inhibition of soluble guanylate cyclase wit h LY-83583. The findings provide pharmacological evidence that hydroge n peroxide and peroxynitrite reversibly dilate cerebral arterioles by activating ATP-sensitive potassium channels, probably through an oxida nt mechanism, whereas superoxide dilates cerebral arterioles by openin g calcium-activated potassium channels. Activation of soluble guanylat e cyclase is not a mediator of the vasodilator action of these agents in cerebral arterioles.