Oxygen radicals in cerebral ischemia.
Superoxide production was measured as the superoxide dismutase (SOD)-inhibitable portion of nitro blue tetrazolium (NBT) reduction after cerebral ischemia-reperfusion in anesthetized cats equipped with cranial windows. Significant superoxide production was found in the early reperfusion period and continued for more than 1 h after ischemia. Superoxide was not detected in control animals not subjected to ischemia, during ischemia, and at 120 min of reperfusion. After ischemia, the vasoconstrictor response to arterial hypocapnia was reduced. This effect was prevented by pretreatment with SOD plus catalase or by deferoxamine. The response to topical acetylcholine was converted to vasoconstriction after ischemia. The normal vasodilator response reappeared spontaneously at 120 min of reperfusion. The vasodilator response to acetylcholine was preserved in animals pretreated with SOD plus catalase. Blood-brain barrier permeability to labeled albumin and horseradish peroxidase was increased after ischemia. These effects were minimized by pretreatment with SOD and catalase. We conclude that superoxide generation occurs during reperfusion after cerebral ischemia for a fairly long period and that superoxide and its derivatives are responsible at least in part for the vasodilation and the abnormal reactivity as well as for the increase in blood-brain barrier permeability to macromolecules seen after ischemia. Furthermore, the findings suggest that the agent responsible for the vascular abnormalities is hydroxyl radical generated via the iron-catalyzed Haber-Weiss reaction.
Nelson
C W
CW
Department of Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Wei
E P
EP
Povlishock
J T
JT
Kontos
H A
HA
Moskowitz
M A
MA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000503:physiopathology; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology*; D002199:Capillary Permeability; D002374:Catalase / Q000494:pharmacology; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects; D006735:Horseradish Peroxidase; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015424:Reperfusion; D013481:Superoxides / Q000378:metabolism / Q000494:pharmacology; D014664:Vasodilation
D017382:Reactive Oxygen Species; D013481:Superoxides; D006735:Horseradish Peroxidase; D002374:Catalase; D000109:Acetylcholine