George E. Brown memorial lecture. Oxygen radicals in cerebral vascular injury.
George E. Brown memorial lecture. Oxygen radicals in cerebral vascular injury.
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乔治·E·布朗纪念演讲。
DOI：
10.1161/01.res.57.4.508
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发表时间：
1985
影响因子：
20.1
通讯作者：
Kontos,HA
中科院分区：
文献类型：
--
作者：
Kontos,HA
动脉血压的急剧升高会导致持续的脑小动脉扩张，对二氧化碳和血压变化的异常反应，取消乙酰胆碱的内皮依赖性扩张，内皮和血管平滑肌的离散形态损害，以及血脑屏障对血浆蛋白的破坏。环氧合酶抑制剂或自由基清除剂可抑制血管的扩张、异常反应性和形态异常。在高血压期间和高血压消退一小时后，都可以检测到应用于脑表面的氮蓝四唑的超氧化物歧化酶抑制的还原。硝基蓝四氮唑的还原也被阴离子通道的抑制剂所还原。局部应用花生四烯酸可复制高血压后出现的异常。这一结果与急性高血压诱导超氧阴离子自由基的产生与环氧合酶加速花生四烯酸代谢有关。这种自由基通过阴离子通道进入脑细胞外空间，产生过氧化氢和羟基自由基。这三种自由基都能通过松弛脑血管平滑肌而引起血管扩张。羟基自由基是血管壁损伤的最有可能的候选者。这一机制在慢性实验性高血压中的意义或与人类疾病的相关性尚不清楚。
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 endothelium and vascular smooth muscle, and breakdown of the blood-brain barrier to plasma proteins. The dilation, abnormal reactivity, and morphological abnormalities are inhibited by pretreatment with cyclooxygenase inhibitors or with free radical scavengers. Superoxide dismutase-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 cyclooxygenase. This radical enters cerebral extracellular 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 muscle. The hydroxyl radical is the most likely candidate for vascular wall damage. The significance of this mechanism in chronic experimental hypertension or its relevance to human disease is not known.