Endothelium-dependent responses after experimental brain injury.
We examined the effect of fluid percussion brain injury on the responses to topical application of acetylcholine and serotonin, two vasoactive agents that have endothelium-dependent effects, in anesthetized cats equipped with cranial windows. Before brain injury, topical acetylcholine dilated both small and large arterioles. Thirty minutes after brain injury, acetylcholine constricted small arterioles, and the vasodilator response of large vessels was abolished. Subsequent application either of superoxide dismutase plus catalase to eliminate superoxide and hydrogen peroxide or of deferoxamine, an agent that scavenges iron and inhibits the production of hydroxyl radical via the Haber-Weiss reaction, restored the normal vasodilator responses to acetylcholine. Serotonin constricted both large and small arterioles before brain injury. After brain injury, small arterioles responded with a small vasodilation, and the response of large arterioles was abolished. After application of superoxide dismutase and catalase, the normal vasoconstrictor response to serotonin was restored. The results show that endothelium-dependent vasodilation from acetylcholine is eliminated by brain injury by a mechanism that involves the generation of oxygen radicals, and, more specifically, the production of hydroxyl radical. The results with serotonin are explained by the elimination by oxygen radicals of a vasoconstrictor agent generated by this agent, perhaps an endothelium-derived contracting factor.
Kontos
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Department of Medicine, Medical College of Virginia, Richmond.
Wei
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D002374:Catalase / Q000494:pharmacology; D002415:Cats; D002560:Cerebrovascular Circulation / Q000502:physiology; D003676:Deferoxamine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005609:Free Radicals; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology; D010100:Oxygen / Q000502:physiology; D010474:Percussion; D012701:Serotonin / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D005609:Free Radicals; D009569:Nitric Oxide; D012701:Serotonin; D002374:Catalase; D013482:Superoxide Dismutase; D003676:Deferoxamine; D000109:Acetylcholine; D010100:Oxygen