Impaired pulmonary conversion of angiotensin I to angiotensin II in rats exposed to chronic hypoxia

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 to 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 < 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 < 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.