Superoxide scavengers do not prevent ischemia-induced alteration of cerebral vasodilation in piglets.
Piglet brains generate superoxide during postischemic reperfusion, and topical application of activated oxygen species alters pial arteriolar responses. We investigated effects of pretreatment with scavengers of superoxide and H2O2 on ischemia-induced alterations of pial arteriolar responses in anesthetized newborn pigs. Four groups were studied: 1) time control, 2) untreated ischemia, 3) ischemia pretreated topically and systemically (conjugated to polyethylene glycol) with superoxide dismutase (SOD) and catalase, and 4) ischemia pretreated with Tiron. Pretreatment with SOD conjugated to polyethylene glycol alone during postischemic reperfusion effectively removed superoxide from its site of generation during postischemic reperfusion, but topical SOD was used also an insurance. Piglets were studied before and after 20 min of total cerebral ischemia caused by maintaining intracranial pressure above mean arterial pressure. As reported previously, before ischemia, hypercapnia and isoproterenol dilated pial arteries and arterioles and hypercapnia but not isoproterenol increased cortical periarachnoid cerebrospinal fluid 6-keto-prostaglandin F1 alpha, measured as an index of cerebral cortical prostacyclin synthesis. After cerebral ischemia, pial arterioles did not dilate in response to hypercapnia and 6-keto-prostaglandin F1 alpha did not increase, but dilation to isoproterenol was unchanged. The present study found that treatment with SOD/catalase or Tiron did not prevent loss of vasodilation to hypercapnia or the loss of hypercapnia-induced cerebral 6-keto-prostaglandin F1 alpha synthesis after cerebral ischemia. The postischemic loss of cerebral vasodilation to hypercapnia does not appear to involve superoxide or a subsequent reduced form of oxygen.
Department of Physiology/Biophysics, University of Tennessee, Memphis 38163.
C W
CW
Leffler
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Thompson
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Armstead
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Mirro
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Shibata
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Busija
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002545:Brain Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D002374:Catalase / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D016166:Free Radical Scavengers; D006935:Hypercapnia / Q000503:physiopathology; D007022:Hypotension / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects
D016166:Free Radical Scavengers; D013481:Superoxides; D015121:6-Ketoprostaglandin F1 alpha; D002374:Catalase; D013482:Superoxide Dismutase; D007545:Isoproterenol