DUAL ROLE OF NITRIC-OXIDE IN FOCAL CEREBRAL-ISCHEMIA
DUAL ROLE OF NITRIC-OXIDE IN FOCAL CEREBRAL-ISCHEMIA
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DOI：
10.1016/0028-3908(94)90048-5
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发表时间：
1994-11-01
影响因子：
4.7
通讯作者：
MOSKOWITZ, MA
中科院分区：
文献类型：
--
作者：
DALKARA, T;YOSHIDA, T;MOSKOWITZ, MA
本实验观察了一氧化氮（NO）在大鼠大脑中动脉闭塞后脑缺血病理生理中的作用。一氧化氮合酶（NOS）活性抑制L-精氨酸类似物，而静脉注射L-精氨酸剂量依赖性地减少梗死体积在相同的模型中，梗死面积显着增加。L-精氨酸给药后的保护作用与梗死周围区内血流增强有关，这一点通过同时记录rCBF和下丘脑内皮质电图活动来证明。7-硝基吲唑（7-NI）的选择性NOS抑制在25和50 mg/kg剂量下显著减少梗死体积，并且其量不降低软膜血管对局部乙酰胆碱的反应。总之，这些数据表明，增强的NO生产内的血管保护脑组织在局灶性缺血通过血流动力学机制，而神经元过度生产可能促进或介导神经毒性。最近使用缺乏NOS活性的转基因动物的数据支持后一个结论。
The importance of nitric oxide (NO) in the pathophysiology of cerebral ischemia was examined following middle cerebral artery occlusion in rats. A significant increase in infarct size developed following inhibition of NO synthase (NOS) activity by L-arginine analogues whereas intravenous L-arginine dose-dependently decreased infarct volume in the same models. Protection after L-arginine administration was associated with enhanced blood flow within the perinfarct zone as demonstrated by simultaneous recording of rCBF and electrocorticogram activity within subjacent brain. Selective NOS inhibition by 7-nitroindazole (7-NI) significantly reduced infarct Volume at doses of 25 and 50 mg/kg and in amounts that did not decrease the response of pial vessels to topical acetylcholine. Together these data suggest that enhanced NO production within the cerebrovasculature protects brain tissue during focal ischemia via hemodynamic mechanisms whereas neuronal overproduction may facilitate or mediate neurotoxicity. Recent data using transgenic animals lacking NOS activity support the latter conclusion.