SUPEROXIDE GENERATION AND REVERSAL OF ACETYLCHOLINE-INDUCED CEREBRAL ARTERIOLAR DILATION AFTER ACUTE HYPERTENSION
SUPEROXIDE GENERATION AND REVERSAL OF ACETYLCHOLINE-INDUCED CEREBRAL ARTERIOLAR DILATION AFTER ACUTE HYPERTENSION
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DOI：
10.1161/01.res.57.5.781
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发表时间：
1985-01-01
影响因子：
20.1
通讯作者：
POVLISHOCK, JT
中科院分区：
文献类型：
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作者：
WEI, EP;KONTOS, HA;POVLISHOCK, JT
在装有颅窗的麻醉猫中，研究了静脉注射去甲肾上腺素引起的急性高血压期间和之后脑细胞外间隙中超氧阴离子自由基的出现。通过证明硝基蓝四唑的超氧化物歧化酶抑制还原的存在来检测超氧化物。硝基蓝四唑的还原超氧化物歧化酶抑制率为4.1±。高血压期间为 1.61 nM/min/cm2，4.55 .+-。高血压消退后一小时为 0.62 nM/min/cm2。在没有高血压的情况下给予去甲肾上腺素期间，硝基蓝四唑的还原超氧化物歧化酶抑制率为0.44±。每平方厘米 0.17 nM/分钟。高血压期间硝基四氮唑的还原也可以通过预先用 pH 10 的苯基乙二醛处理大脑表面来抑制，从而诱导阴离子通道的不可逆抑制。结果表明，急性高血压与超氧化物的产生有关，超氧化物通过阴离子通道进入大脑细胞外空间。高血压后，局部应用超氧化物歧化酶和过氧化氢酶可显着抑制急性高血压引起的持续血管舒张，这表明其部分归因于超氧化物和源自超氧化物的其他自由基。脑小动脉对局部乙酰胆碱的血管舒张反应在急性高血压后转变为血管收缩，并在局部应用超氧化物歧化酶和过氧化氢酶后恢复为血管舒张。结果表明，急性高血压后产生的超氧化物和其他自由基会干扰乙酰胆碱诱导的内皮依赖性血管舒张，可能是因为它们破坏了内皮衍生的舒张因子。
The appearance of superoxide anion radical in cerebral extracellular space during and after acute hypertension induced by intravenous norepinephrine was investigated in anesthetized cats equipped with cranial windows. Superoxide was detected by demonstrating the presence of superoxide dismutase-inhibitable reduction of nitroblue tetrazolium. The superoxide dismutase-inhibitable rate of reduction of nitroblue tetrazolium was 4.1 .+-. 1.61 nM/min per cm2 during hypertension and 4.55 .+-. 0.62 nM/min per cm2 one hour after hypertension had subsided. During norepinephrine administration in the absence of hypertension, the superoxide dismutase-inhibitable rate of reduction of nitroblue tetrazolium was 0.44 .+-. 0.17 nM/min per cm2. The reduction of nitroblue tetrazolium during hypertension was also inhibited by prior treatment of the brain surface with phenylglyoxal at pH 10, to induce irreversible inhibition of the anion channel. The results show that acute hypertension is associated with the generation of superoxide which enters the extracellular space of the brain via the anion channel. Following hypertension, the sustained vasodilation caused by acute hypertension was inhibited significantly by topical application of superoxide dismutase and catalase, showing that it was due in part to superoxide and other radicals derived from it. The vasodilator response of cerebral arterioles to topical acetylcholine was converted to vasoconstriction following acute hypertension, and restored to vasodilation following topical application of superoxide dismutase and catalase. The results show that superoxide and other radicals generated after acute hypertension interfere with acetylcholine-induced endothelium-dependent vasodilation, probably because they destroy the endothelium derived relaxant factor.