Impaired pulmonary conversion of angiotensin I to angiotensin II in rats exposed to chronic hypoxia.
Impaired pulmonary conversion of angiotensin I to angiotensin II in rats exposed to chronic hypoxia.
复制标题
慢性缺氧大鼠肺部血管紧张素 I 向血管紧张素 II 的转化受损。
DOI：
10.1152/jappl.1986.60.4.1121
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Oparil,S
中科院分区：
文献类型：
--
作者：
Jackson,RM;Narkates,AJ;Oparil,S
使用恒流灌注的离体大鼠肺制剂检查将大鼠暴露在正常大气压下的缺氧环境 21-24 天对肺内血管紧张素 I (ANG I) 转化为血管紧张素 II (ANG II) 的影响。将 125I-ANG I (160 fmol) 单独注射，并与分级剂量（0.1、1.0 和 100 nmol）未标记的 ANG I 一起注射到肺动脉中，收集流出物用于测量 ANG I、ANG II 和代谢物。在低剂量注射ANG I（单独125I-ANG I或与0.1或1.0 nmol未标记ANG I）时，在21天缺氧暴露的动物中，ANG I向ANG II的转化百分比为67.5+/-2.1（SE）、65.1+/-2.0和62.5+/-1.6，以及83.8+/-2.7，维持在常氧条件下的对照大鼠为 81.4 +/- 3.9 和 79.6 +/- 2.3（P 小于 0.01）。在注射 ANG I 的最高剂量（100 nmol）时，缺氧组和对照组的转化百分比分别降低至 46.8 +/- 5.0 和 64.0 +/- 6.0（P 小于 0.05）。在任何 ANG I 负荷下，缺氧肺与常氧肺中标记物质通过肺循环的平均通过时间没有显着差异，这表明缺氧肺中观察到的转化减少与底物暴露动力学的改变无关。因此，慢性缺氧与跨肺 ANG I 转化的显着抑制相关，该转化与灌注液流量无关。我们假设这种现象是由于内皮膜水平的改变所致。
The effects of exposing rats to hypoxia at normal atmospheric pressure for periods of 21–24 days on intrapulmonary conversion of angiotensin I (ANG I) to angiotensin II (ANG II) were examined using an isolated rat lung preparation perfused at constant flow. 125I-ANG I (160 fmol) was injected alone and with graded doses (0.1, 1.0, and 100 nmol) of unlabeled ANG I into the pulmonary artery, and the effluent was collected for measurement of ANG I, ANG II, and metabolites. At low doses of injected ANG I (125I-ANG I alone or with 0.1 or 1.0 nmol unlabeled ANG I), the percent conversion of ANG I to ANG II was 67.5 +/- 2.1 (SE), 65.1 +/- 2.0, and 62.5 +/- 1.6 in 21-day hypoxia-exposed animals and 83.8 +/- 2.7, 81.4 +/- 3.9, and 79.6 +/- 2.3 (P less than 0.01) in control rats maintained under normoxic conditions. At the highest dose (100 nmol) of injected ANG I, percent conversion was reduced in both hypoxic and control groups to 46.8 +/- 5.0 and 64.0 +/- 6.0, respectively (P less than 0.05). Mean transit times of labeled material through the pulmonary circulation were not significantly different in hypoxic vs. normoxic lungs at any ANG I load, suggesting that the decreased conversion seen in hypoxic lungs was not related to altered kinetics of substrate exposure. Thus chronic hypoxia is associated with significant inhibition of transpulmonary ANG I conversion that is independent of perfusate flow. We postulate that this phenomenon is due to alterations at the endothelial membrane level.