Endothelial dysfunction coincides with an enhanced nitric oxide synthase expression and superoxide anion production
Endothelial dysfunction coincides with an enhanced nitric oxide synthase expression and superoxide anion production
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DOI：
10.1161/01.hyp.30.4.934
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发表时间：
1997-10-01
期刊：
影响因子：
8.3
通讯作者：
Busse, R
中科院分区：
文献类型：
--
作者：
Bouloumie, A;Bauersachs, J;Busse, R
我们研究了主动脉结扎诱导的高血压对SD大鼠主动脉和冠状动脉循环中内皮依赖性血管舒张反应的影响。我们研究了高血压对内皮型一氧化氮合酶（NOS III）表达的影响，通过Western印迹和逆转录聚合酶链反应实验进行评估，并对超氧阴离子（O-2（-））的生产。主动脉结扎后两周，内皮依赖性舒张功能没有改变。此时，NOS III在主动脉和汇合的冠状动脉微血管内皮细胞（RCMECs）中的表达没有显示出明显的变化，而O-2（-）的产生增加了1.9倍，在动脉结扎大鼠的动脉瘤中。主动脉结扎后6周，心脏（减少50%）和主动脉（减少35%）的内皮依赖性扩张明显受损。NOS III蛋白和mRNA水平的分析显示，显着增加，在两个arrhetas和融合RCMECs（2.6至4倍）前arrhetic-banded与sharn操作的大鼠相比。结扎大鼠主动脉和汇合的RCMECs中O-2（-）的产生没有进一步增加。增强硝基酪氨酸蛋白水平也检测到在主动脉从6周的结扎大鼠。这些发现表明，在主动脉缩窄引起的高血压中，仅增加O-2（-）的产生不足以产生内皮功能障碍。只有当NOS III表达和O-2（-）产生增加时，才观察到内皮血管扩张剂低反应性，并与硝基酪氨酸残基增加有关。这表明内皮功能障碍的发展与可能导致过氧亚硝酸盐形成的不是一种而是两种内皮衍生自由基的过度产生有关。
We investigated the effects of aortic banding-induced hypertension on the endothelium-dependent vasodilator responses in the aorta and coronary circulation of Sprague-Dawley rats. We studied the influence of hypertension on the endothelial nitric oxide synthase (NOS III) expression, assessed by Western blot and reverse transcription-polymerase chain reactions experiments, and on the superoxide anion (O-2(-)) production. Two weeks after aortic banding, the endothelium-dependent relaxations were not altered. At this time, the expression of NOS III in the aorta and in confluent coronary microvascular endothelial cells (RCMECs) exhibited no marked changes, whereas O-2(-) production was enhanced 1.9-fold in aortas from aortic-banded rats. Six weeks after aortic banding, the endothelium-dependent dilations were markedly impaired in the heart (50% decrease) and aorta (35% decrease). Analysis of NOS III protein and mRNA levels revealed marked increases in both aortas and confluent RCMECs (2.6- to 4-fold) front aortic-banded compared with sharn-operated rats. There was no further increase in O-2(-) production in both the aorta and confluent RCMECs from aortic-banded rats. An enhanced nitrotyrosine protein level was also detected in the aorta from 6-week aortic-banded rats. These findings indicate that in hypertension induced by aortic banding, an enhanced O-2(-) production alone is not sufficient to produce endothelial dysfunction. Endothelial vasodilator hyporesponsiveness was observed only when NOS III expression and O-2(-) production were increased and was associated with the appearance of enhanced nitrotyrosine residues. This would suggest that the development of endothelial dysfunction is linked to an overproduction of not one, but two, endothelium-derived radicals that might lead to the formation of peroxynitrite.