Peroxynitrite is a contractile agonist of cerebral artery smooth muscle cells
Peroxynitrite is a contractile agonist of cerebral artery smooth muscle cells
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DOI：
10.1152/ajpheart.1998.275.5.h1585
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发表时间：
1998-11-01
影响因子：
4.8
通讯作者：
Brzezinska, AK
中科院分区：
文献类型：
--
作者：
Elliott, SJ;Lacey, DJ;Brzezinska, AK
在缺血组织的再灌注时，发生延长的血管收缩阶段，其机制知之甚少。然而，已知在再灌注期间形成过氧亚硝酸根（ONOO-）。本实验观察了ONOO-对Wistar大鼠大脑中动脉的收缩作用。ONOO-对血管直径的影响呈剂量依赖性。低剂量ONOO-（10 μ M）导致血管收缩15%。在25 μ M的中间浓度，ONOO-的效果是可变的，而在最高浓度（100 μ M），血管进行持续扩张，并成为不敏感的内源性血管收缩剂B-羟色胺。在单细胞水平，ONOO-引起脑动脉平滑肌细胞收缩。还原型谷胱甘肽完全抑制ONOO-对单个细胞的收缩作用，但不抑制氧化型谷胱甘肽。媒介物和分解的ONOO-各自对细胞长度的影响最小。这些数据表明，ONOO-是大脑中动脉的收缩激动剂，在单细胞和整个血管水平，这表明ONOO-的形成可能有助于脑卒中缺血性脑损伤的机制。此外，相对高浓度的ONOO-导致血管麻痹。
On reperfusion of ischemic tissue, a prolonged phase of vasoconstriction occurs, the mechanism of which is poorly understood. however, it is known that peroxynitrite (ONOO-) is formed during reperfusion. In this study the contractile properties of ONOO- were investigated in Wistar rat middle cerebral arteries. The effects of ONOO- on vessel diameter were dose dependent. Low-dose ONOO- (10 mu M) caused vessels to constrict by 15%. At an intermediate concentration of 25 mu M, the effect of ONOO- was variable, whereas at the highest concentration (100 mu M), vessels underwent persistent dilation and became insensitive to the endogenous vasoconstrictor B-hydroxytryptamine. At the single cell level, ONOO- caused cerebral artery smooth muscle cells to contract. Reduced, but not oxidized, glutathione completely inhibited the contractile action of ONOO- on single cells. Vehicle and decomposed ONOO- each had minimal effect on cell length. These data show that ONOO- is a contractile agonist of middle cerebral arteries, at the single cell and whole vessel levels, suggesting that formation of ONOO- may contribute mechanistically to ischemic brain injury during stroke. Moreover, relatively high concentrations of ONOO- result in vascular paralysis.