摘要：

Acute, severe increases in arterial blood pressure cause sustained cerebral arteriolar dilation, abnormal reactivity to carbon dioxide and to changes in blood pressure, abolition of endothelium-dependent dilation from acetylcholine, discrete morphological lesions of the endo- thelium and vascular smooth muscle, and breakdown of the blood-brain barrier to plasma proteins. The dilation, abnormal reactivity, and morphological abnormalities are inhibited by prerreatment with cydooxygenase inhibitors or with free radical scavengers. Superoxide dismu- tase-inhibitable reduction of nitroblue tetrazolium applied to the brain surface was detectable both during hypertension and one hour after hypertension subsided. Nitroblue tetrazolium reduction is also reduced by inhibitors of the anion channel. The abnormalities seen after hypertension are reproduced by topical application of arachidonate. The results are consistent with the view that acute hypertension induces generation of superoxide anion radical in association with accelerated arachidonate metabolism via cydooxygenase. This radical enters cerebral extra- cellular space via the anion channel and gives rise to hydrogen peroxide and hydroxyl radical. All three radicals are capable of causing vasodilation by relaxation of cerebral vascular smooth musde. The hydroxyl radical is the most likely candidate for vascular wall damage. The signifi- cance of this mechanism in chronic experimental hypertension or its relevance to human disease is not known. (Circ Res 57: 508-516, 1985) THE sequential univalent reduction of oxygen pro- duces a number of reactive intermediate species. These include superoxide anion radical, hydrogen peroxide, and the hydroxyl radical. Superoxide and hydrogen peroxide are normal products of several enzymatic reactions. Superoxide is produced by mi- tochondria (Boveris, 1977) and by certain oxidative enzymes, such as xanthine oxidase (McCord and Fridovich, 1968) and cytochrome P-450 reductase (Kuthan and Ullrich, 1982). It is also produced by leukocytes via a NADPH-dependent oxidase (Ba- bior, 1978). Hydrogen peroxide can be produced directly by oxidative enzymes such as xanthine oxi- dase, or it can be generated by the spontaneous or catalyzed dismutation of superoxide. The hydroxyl radical can be produced directly in biological fluids, under certain circumstances, such as under the in- fluence of radiation. A more likely source for this radical is the interaction of superoxide and hydrogen peroxide, via the Haber-Weiss reaction (Haber and Weiss, 1934). The uncatalyzed Haber-Weiss reaction proceeds at a very slow rate under the conditions prevalent in biological materials. However, in the presence of catalytic iron, the reaction can proceed at a sufficiently fast rate to generate significant

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