Oxygen radicals and vascular damage.
The effects of topical application of agents which produce oxygen radicals on cerebral arterioles were studied in anesthetized cats. Xanthine oxidase plus xanthine, which produced superoxide anion radical, hydrogen peroxide, and hydrogen peroxide plus ferrous sulfate, which produced the free hydroxyl radical, induced sustained dilation, reduced responsiveness to the vasoconstrictor effect of hypocapnia, and destructive lesions of the endothelium and of the vascular smooth muscle. Similar effects were produced by arachidonate, 15-HPETE, and PGG2. The effect of arachidonate was inhibited by mannitol, a free hydroxyl radical scavenger, the effect of PGG2 was inhibited by SOD, the effect of 15-HPETE was inhibited by either catalase or SOD. These results suggest that these cerebral vascular abnormalities were produced by a single destructive free radical, probably the hydroxyl free radical, generated via interaction of superoxide and hydrogen peroxide. Cerebral vascular abnormalities similar to those produced by oxygen radicals were also seen after experimental concussive brain injury or after acute hypertension. After brain injury, activation of phospholipase C and increased brain prostaglandin concentration were demonstrated. The vascular effects of brain injury and acute hypertension were inhibited by free radical scavengers. The results suggest that, in these conditions, vascular damage is induced by oxygen radicals generated from arachidonate in association with increased prostaglandin synthesis.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000008:administration & dosage; D001930:Brain Injuries / Q000378:metabolism; D002415:Cats; D002417:Cattle; D002536:Cerebral Arteries / Q000293:injuries* / Q000378:metabolism / Q000503:physiopathology; D005609:Free Radicals; D006973:Hypertension / Q000378:metabolism; D015289:Leukotrienes; D008054:Lipid Peroxides / Q000008:administration & dosage; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010101:Oxygen Consumption; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D014666:Vasomotor System / Q000187:drug effects; D014969:Xanthine Oxidase / Q000008:administration & dosage
D001095:Arachidonic Acids; D005609:Free Radicals; D015289:Leukotrienes; D008054:Lipid Peroxides; D016718:Arachidonic Acid; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D014969:Xanthine Oxidase