Mechanisms of cerebral vasodilation by superoxide, hydrogen peroxide, and peroxynitrite. 1996

E P Wei, and H A Kontos, and J S Beckman
Department of Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.

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 that 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 that 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 LY-83583. 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, whereas 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.

UI MeSH Term Description Entries
D009566 Nitrates Inorganic or organic salts and esters of nitric acid. These compounds contain the NO3- radical. Nitrate
D002415 Cats The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801) Felis catus,Felis domesticus,Domestic Cats,Felis domestica,Felis sylvestris catus,Cat,Cat, Domestic,Cats, Domestic,Domestic Cat
D002560 Cerebrovascular Circulation The circulation of blood through the BLOOD VESSELS of the BRAIN. Brain Blood Flow,Regional Cerebral Blood Flow,Cerebral Blood Flow,Cerebral Circulation,Cerebral Perfusion Pressure,Circulation, Cerebrovascular,Blood Flow, Brain,Blood Flow, Cerebral,Brain Blood Flows,Cerebral Blood Flows,Cerebral Circulations,Cerebral Perfusion Pressures,Circulation, Cerebral,Flow, Brain Blood,Flow, Cerebral Blood,Perfusion Pressure, Cerebral,Pressure, Cerebral Perfusion
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005905 Glyburide An antidiabetic sulfonylurea derivative with actions like those of chlorpropamide Glibenclamide,Daonil,Diabeta,Euglucon 5,Euglucon N,Glybenclamide,HB-419,HB-420,Maninil,Micronase,Neogluconin,HB 419,HB 420,HB419,HB420
D006861 Hydrogen Peroxide A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. Hydrogen Peroxide (H2O2),Hydroperoxide,Oxydol,Perhydrol,Superoxol,Peroxide, Hydrogen
D000634 Aminoquinolines Quinolines substituted in any position by one or more amino groups.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001160 Arterioles The smallest divisions of the arteries located between the muscular arteries and the capillaries. Arteriole
D001696 Biomechanical Phenomena The properties, processes, and behavior of biological systems under the action of mechanical forces. Biomechanics,Kinematics,Biomechanic Phenomena,Mechanobiological Phenomena,Biomechanic,Biomechanic Phenomenas,Phenomena, Biomechanic,Phenomena, Biomechanical,Phenomena, Mechanobiological,Phenomenas, Biomechanic

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