Upregulation of nitric oxide synthase correlates temporally with onset of pulmonary vascular remodeling in the hypoxic rat
Upregulation of nitric oxide synthase correlates temporally with onset of pulmonary vascular remodeling in the hypoxic rat
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DOI：
10.1161/01.hyp.28.5.743
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发表时间：
1996-11-01
期刊：
影响因子：
8.3
通讯作者：
Johns, RA
中科院分区：
文献类型：
--
作者：
Xue, C;Johns, RA
一氧化氮信号的改变已被假设在低氧性肺动脉高压的发展中具有病因学作用。然而，缺氧肺中一氧化氮合酶（NOS）表达的变化仍存在争议。在本研究中，我们使用(1)Northern和Western分析来测量NOS mRNA和蛋白的表达，(2)肺组织学结合肺和心脏重量测量来监测肺血管重构，(3)免疫组织化学来定位NOS蛋白。结果表明，缺氧1 ~ 7天后，内皮细胞NOS mRNA和蛋白表达上调，这在时间上与缺氧肺动脉高压发展过程中发生的血管重构相关。缺氧还可诱导支气管上皮细胞内NOS的表达和血管平滑肌内NOS的表达，但不影响巨噬细胞内NOS的表达和肺组织内NOS的活性。这些结果表明，内皮细胞NOS的上调与缺氧引起的血管重构密切相关，提示一氧化氮在肺动脉高压的发生中起一定作用。
Alterations in nitric oxide signaling have been hypothesized to have an etiologic role in the development of hypoxic pulmonary hypertension. However, changes in the expression of nitric oxide synthase (NOS) in hypoxic lungs remains controversial. In this study, we used (1) Northern and Western analyses to measure NOS mRNA and protein expressions, (2) lung histology together with measurements of lung and heart weights to monitor pulmonary vascular remodeling, and (3) immunohistochemistry to localize NOS proteins. The data demonstrated that endothelial NOS mRNA and protein were upregulated over 1 to 7 days of hypoxia that temporally correlated with and preceded the vascular remodeling that occurred in the course of the development of hypoxic pulmonary hypertension. Hypoxia also induced brain NOS in bronchial epithelium and inducible NOS in vascular smooth muscle but did not affect inducible NOS expression in macrophages or basal guanylyl cyclase activity in the lung. These findings showed that upregulation of endothelial NOS was tightly correlated with the vascular remodeling induced by hypoxia, suggesting a role for nitric oxide in the development of pulmonary hypertension.