Reduced hypoxic pulmonary vascular remodeling by nitric oxide from the endothelium
Reduced hypoxic pulmonary vascular remodeling by nitric oxide from the endothelium
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DOI：
10.1161/01.hyp.37.2.322
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发表时间：
2001-02-01
期刊：
影响因子：
8.3
通讯作者：
Yokoyama, M
中科院分区：
文献类型：
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作者：
Ozaki, M;Kawashima, S;Yokoyama, M
我们研究了是否内源性一氧化氮（NO）的过度生产可以防止缺氧诱导的肺动脉高压和血管重构，通过使用内皮NO过表达（eNOS-Tg）小鼠。将雄性eNOS-Tg小鼠及其同窝出生的小鼠（野生型，WT）在常氧或10%低氧条件下维持3周。在常氧条件下，eNOS-Tg小鼠肺组织中eNOS蛋白水平、Ca 2+依赖性NOS活性和cGMP水平均高于WT小鼠。eNOS活性和cGMP的生产在肺中没有改变显着的缺氧暴露在任何基因型。慢性缺氧不诱导iNOS的表达，也不增加其活性在任何基因型，血浆和肺内皮素-1水平增加慢性缺氧，但这些水平之间没有显着差异的基因型。在血流动力学分析中，eNOS-Tg小鼠的右心室收缩压（RVSP）与常氧下WT小鼠相似。慢性缺氧增加RVSP和诱导右心室肥大，但这些增加的程度在eNOS-Tg小鼠明显较小。组织学检查显示，缺氧小鼠肺动脉中膜壁增厚。而小动脉管壁增厚（直径
We examined whether overproduction of endogenous nitric oxide (NO) can prevent hypoxia-induced pulmonary hypertension and vascular remodeling by using endothelial NO-overexpressing (eNOS-Tg) mice. Male eNOS-Tg mice and their littermates (wild-type, WT) were maintained in normoxic or 10% hypoxic condition for 3 weeks. In normoxia, eNOS protein levels, Ca2+-dependent NOS activity, and cGMP levels in the lung of eNOS-Tg mice were higher than those of WT mice. Activity of eNOS and cGMP production in the lung did not change significantly by hypoxic exposure in either genotype. Chronic hypoxia did not induce iNOS expression nor increase its activity in either genotype, Plasma and lung endothelin-1 levels were increased by chronic hypoxia, but these levels were not significantly different between the 2 genotypes. In hemodynamic analysis, right ventricular systolic pressure (RVSP) in eNOS-Tg mice was similar to that in WT mice in normoxia. Chronic hypoxia increased RVSP and induced right ventricular hypertrophy in both genotypes; however, the degrees of these increases were significantly smaller in eNOS-Tg mice, Histological examination revealed that hypoxic mice showed medial wall thickening in pulmonary arteries. However, the increase of the wall thickening in small arteries (diameter