Augmentation of nitric oxide, superoxide, and peroxynitrite production during cerebral ischemia and reperfusion in the rat
Augmentation of nitric oxide, superoxide, and peroxynitrite production during cerebral ischemia and reperfusion in the rat
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DOI：
10.1023/a:1022468522564
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发表时间：
1998-02-01
影响因子：
4.4
通讯作者：
Wong, PYK
中科院分区：
文献类型：
--
作者：
Forman, LJ;Liu, P;Wong, PYK
观察双侧颈总动脉闭塞30 min后再灌注4 h对大鼠大脑半球总一氧化氮合酶（NOS）和诱导型一氧化氮合酶（NOS）活性以及一氧化氮（NO）、超氧化物和过氧亚硝酸盐生成的影响。与假手术对照组相比，脑缺血再灌注导致脑半球总一氧化氮和诱导一氧化氮活性显著增加，脑半球一氧化氮和超氧化物的产生显著增加。血浆NO水平和外周血白细胞计数均显著升高。免疫组化染色检测硝基酪氨酸（一种过氧亚硝酸盐生成的标志物）显示缺血再灌注导致脑过氧亚硝酸盐合成增加。给予不可逆的NOS抑制剂n -omega-硝基- l -精氨酸（L-NA），增加了大脑中的超氧化物水平，显著降低了血浆NO。L-NA使大鼠大脑半球总一氧化氮和诱导一氧化氮活性以及一氧化氮和免疫反应性硝基酪氨酸活性降低。血浆中白细胞的数量不受L-NA的影响。这些发现表明，脑缺血-再灌注导致大脑半球活性氧的产生增加，过氧亚硝酸盐的产生，而不是超氧化物的产生，可能取决于一氧化氮的可用性。
The effect of ischemia produced by bilateral occlusion of the common carotid arteries (30 min) followed by 4 hours of reperfusion on total and inducible nitric oxide synthase (NOS) activity and the production of nitric oxide (NO), superoxide and peroxynitrite in the cerebral hemispheres was determined in the rat. Compared to sham-operated controls, cerebral ischemia-reperfusion resulted in a significant increase in total and inducible NOS activity and a significant increase in the production of NO and superoxide in the cerebral hemispheres. The level of NO in the plasma and the peripheral leukocyte count were also significantly increased. Immunohistochemical staining for nitrotyrosine (a marker of peroxynitrite production) showed that ischemia-reperfusion resulted in increased synthesis of cerebral peroxynitrite. Administration of the irreversible NOS inhibitor, N-omega-nitro-L-arginine (L-NA), increased superoxide levels in the brain and significantly reduced plasma NO. Total and inducible NOS activity as well as NO and immunoreactive nitrotyrosine, in the cerebral hemispheres were reduced with L-NA administration. The number of leukocytes in the plasma was unaffected by administration of L-NA. These findings suggest that cerebral ischemia-reperfusion causes increased production of reactive oxygen species in the cerebral hemispheres and that the production of peroxynitrite, and not superoxide, may be dependent upon the availability of NO.