Vascular remodeling and ET-1 expression in rat strains with different responses to chronic hypoxia
Vascular remodeling and ET-1 expression in rat strains with different responses to chronic hypoxia
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DOI：
10.1152/ajplung.2000.278.5.l981
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发表时间：
2000-05-01
影响因子：
4.9
通讯作者：
Wilkins, MR
中科院分区：
文献类型：
--
作者：
Aguirre, JI;Morrell, NW;Wilkins, MR
慢性缺氧导致Wistar-Kyoto （WKY）大鼠比Fischer 344 （F-344）大鼠更大程度的肺动脉高压。我们质疑这种差异是否与肺动脉解剖结构的基线差异、WKY大鼠更大程度的缺氧诱导的肺血管重构和/或内皮素(ET)-1表达的差异有关。将雄性F-344大鼠和WKY大鼠分别置于常氧或常压低氧条件下维持21 d。形态测量显示，两个菌株的基线肺动脉解剖结构相似。然而，在慢性缺氧期间，WKY大鼠的小肺动脉肌肉化程度更高。基线血浆和肺免疫反应ET-1水平在WKY和F-344大鼠中相似，在WKY大鼠缺氧期间显著升高。Northern分析显示，两种菌株在缺氧期间肺preproET-1 mRNA增加，WKY大鼠增加更大。免疫染色显示缺氧时支气管上皮和肺动脉外周ET-1升高，尽管在WKY大鼠中程度更大。我们得出结论，与F-344菌株相比，WKY菌株对缺氧诱导的肺血管重构的易感性增加，缺氧时肺和循环ET-1水平的增加可能部分解释了这种差异。
Chronic hypoxia leads to a greater degree of pulmonary hypertension in the Wistar-Kyoto (WKY) rat than in the Fischer 344 (F-344) rat. We questioned whether this difference is associated with baseline differences in pulmonary artery anatomy, a greater degree of hypoxia-induced pulmonary vascular remodeling in the WKY rat, and/or differences in expression of endothelin (ET)-1. Male F-344 and WKY rats were maintained in normoxia or normobaric hypoxia for 21 days. Morphometry revealed that baseline pulmonary artery anatomy was similar in the two strains. However, during chronic hypoxia, the WKY rats developed a greater degree of muscularization of small pulmonary arteries. Baseline plasma and lung immunoreactive ET-1 levels were similar in the WKY and F-344 rats and increased significantly during hypoxia in the WKY rats. Northern analysis demonstrated increased lung preproET-1 mRNA during hypoxia in both strains, with a greater increase in WKY rats. Immunostaining demonstrated increased ET-1 in bronchial epithelium and peripheral pulmonary arteries dining hypoxia, although to a greater degree in the WKY rats. We conclude that the WKY strain demonstrates increased susceptibility to hypoxia-induced pulmonary vascular remodeling compared with the F-344 strain and that increased lung and circulating ET-1 levels during hypoxia may partly explain this difference.