eNOS-deficient mice show reduced pulmonary vascular proliferation and remodeling to chronic hypoxia
eNOS-deficient mice show reduced pulmonary vascular proliferation and remodeling to chronic hypoxia
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DOI：
10.1152/ajplung.2000.279.4.l641
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发表时间：
2000-10-01
影响因子：
4.9
通讯作者：
Johns, RA
中科院分区：
文献类型：
--
作者：
Quinlan, TR;Li, DC;Johns, RA
肺动脉高压的特征是肺血管系统的结构和形态变化。为了确定一氧化氮在缺氧诱导的血管重塑中的潜在作用，我们将野生型 [WT(+/+)] 和内皮型一氧化氮合酶 (eNOS) 缺陷 [(-/-)] 小鼠暴露在常氧或缺氧 (10% O-2) 中 2、4 和 6 天或 3 周。平滑肌 α-肌动蛋白和血管性血友病因子免疫组织化学显示，在早期时间点，缺氧 eNOS(-/-) 小鼠肺部的小血管肌肉化程度明显低于 WT(+/+) 小鼠肺部，这一发现与缺氧 4 和 6 天时血管细胞增殖（5-溴-2'-脱氧尿苷阳性）的减少相关。 eNOS(-/-) 小鼠。缺氧 3 周后，两种小鼠都表现出相似的肌肉化小血管百分比；然而，只有WT(+/+)小鼠表现出完全肌肉化血管百分比的增加和血管壁厚度的增加。在所有检查时间点，低氧 WT(+/+) 小鼠肺匀浆中 eNOS 蛋白表达均增加，3 周后表达 eNOS 蛋白的小血管百分比显着增加。这些结果表明，eNOS 缺乏会导致缺氧时小肺血管的肌肉化减少，这可能是由于在这些小鼠中观察到的血管细胞增殖减少所致。
Pulmonary hypertension is characterized by structural and morphological changes to the lung vasculature. To determine the potential role of nitric oxide in the vascular remodeling induced by hypoxia, we exposed wild-type [WT(+/+)] and endothelial nitric oxide synthase (eNOS)-deficient [(-/-)] mice to normoxia or hypoxia (10% O-2) for 2, 4, and 6 days or for 3 wk. Smooth muscle alpha-actin and von Willebrand factor immunohistochemistry revealed significantly less muscularization of small vessels in hypoxic eNOS(-/-) mouse lungs than in WT(+/+) mouse lungs at early time points, a finding that correlated with decreases in proliferating vascular cells (5-bromo- 2'-deoxyuridine positive) at 4 and 6 days of hypoxia in the eNOS(-/-) mice. After 3 wk of hypoxia, both mouse types exhibited similar percentages of muscularized small vessels; however, only the WT(+/+) mice exhibited an increase in the percentage of fully muscularized vessels and increased vessel wall thickness. eNOS protein expression was increased in hypoxic WT(+/+) mouse lung homogenates at all time points examined, with significantly increased percentages of small vessels expressing eNOS protein after 3 wk. These results indicate that eNOS deficiency causes decreased muscularization of small pulmonary vessels in hypoxia, likely attributable to the decrease in vascular cell proliferation observed in these mice.