Enlarged infarcts in endothelial nitric oxide synthase knockout mice are attenuated by nitro-L-arginine
Enlarged infarcts in endothelial nitric oxide synthase knockout mice are attenuated by nitro-L-arginine
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DOI：
10.1097/00004647-199609000-00023
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发表时间：
1996-09-01
影响因子：
6.3
通讯作者：
Moskowitz, MA
中科院分区：
文献类型：
--
作者：
Huang, ZH;Huang, PL;Moskowitz, MA
在内皮型一氧化氮合酶（eNOS）亚型基因缺陷的小鼠大脑中动脉（MCA）闭塞后24小时，测量颅内压大小和血管血流动力学。内皮型一氧化氮合酶突变小鼠发展更大的梗死（21%）比野生型菌株时，评估后24小时管腔内细丝闭塞。此外，局部CBF值记录在大脑中动脉领域的激光多普勒血流仪更严重地减少闭塞后，不成比例地减少在控制性出血性低血压的自动调节实验。与野生型小鼠的情况不同，硝基-L-精氨酸灌流（1 mM）扩张了eNOS敲除小鼠的软脑膜小动脉在一个封闭的颅窗准备。如前所述，eNOS突变小鼠是高血压的。然而，尽管肼苯哒嗪治疗将血压降低至正常血压水平，但梗死面积仍在增加。全身给予硝基-L-精氨酸可降低eNOS突变小鼠的梗死面积（24%），但在野生型小鼠中则不然。这一发现补充了公开的数据，该数据显示硝基-L-精氨酸增加表达eNOS但不表达神经元NOS同种型（即，神经元NOS敲除小鼠）。我们的结论是，内皮细胞内的NO生产可能会保护脑组织，可能是通过血液动力学机制，而神经元NO过度生产可能会导致神经毒性。
Infarct size and vascular hemodynamics were measured 24 h after middle cerebral artery (MCA) occlusion in mice genetically deficient in the endothelial nitric oxide synthase (eNOS) isoform. eNOS mutant mice developed larger infarcts (21%) than the wild-type strain when assessed 24 h after intraluminal filament occlusion. Moreover, regional CBF values recorded in the MCA territory by laser-Doppler flowmetry were more severely reduced after occlusion and were disproportionately reduced during controlled hemorrhagic hypotension in autoregulation experiments. Unlike the situation in wildtype mice, nitro-L-arginine superfusion (1 mM) dilated pial arterioles of eNOS knockout mice in a closed cranial window preparation. As noted previously, eNOS mutant mice were hypertensive. However, infarct size remained increased despite lowering blood pressure to normotensive levels by hydralazine treatment, Systemic administration of nitro-L-arginine decreased infarct size in eNOS mutant mice (24%) but not in the wild-type strain. This finding complements published data showing that nitro-L-arginine increases infarct size in knockout mice expressing the eNOS but not the neuronal NOS isoform (i.e., neuronal NOS knockout mice). We conclude that NO production within endothelium may protect brain tissue, perhaps by hemodynamic mechanisms, whereas neuronal NO overproduction may lead to neurotoxicity.