Wei E P, Kontos H A, Christman C W, DeWitt D S, Povlishock J T
Circ Res. 1985 Nov;57(5):781-7. doi: 10.1161/01.res.57.5.781.
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.
在配备颅窗的麻醉猫中，研究了静脉注射去甲肾上腺素诱导急性高血压期间及之后脑细胞外空间中超氧阴离子自由基的出现情况。通过证明超氧化物歧化酶可抑制的硝基蓝四唑还原反应来检测超氧化物。高血压期间，硝基蓝四唑的超氧化物歧化酶可抑制还原速率为每平方厘米4.1±1.61纳摩尔/分钟，高血压消退一小时后为每平方厘米4.55±0.62纳摩尔/分钟。在无高血压的情况下给予去甲肾上腺素时，硝基蓝四唑的超氧化物歧化酶可抑制还原速率为每平方厘米0.44±0.17纳摩尔/分钟。在高血压期间，硝基蓝四唑的还原反应也可被在pH值为10的条件下用苯乙二醛预处理脑表面以诱导阴离子通道的不可逆抑制所抑制。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脑的细胞外空间。高血压后，急性高血压引起的持续性血管舒张被局部应用超氧化物歧化酶和过氧化氢酶显著抑制，表明其部分原因是超氧化物及其衍生的其他自由基。急性高血压后脑小动脉对局部乙酰胆碱的血管舒张反应转变为血管收缩，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。
