This study investigated the effects of
hypoxia adaptation (10% O2 for 4 days) on rat lung
angiotensin-converting enzyme (ACE) content before and after
hyperoxia exposure (greater than 95% O2 for 2 days). The rationale for this investigation was that
hyperoxia exposure decreases lung ACE, while
hypoxia adaptation produces tolerance (improved survival) to
oxygen toxicity in rats. Rats were exposed to air,
hypoxia,
hyperoxia alone, or
hypoxia followed immediately by
hyperoxia. The lungs were then excised and perfused in vitro at 12 ml/min with
buffer. Lung ACE content was quantitated by measuring the single-pass binding of an iodinated
ACE inhibitor, 125I-MK 351A, a derivative of
lisinopril. We showed previously that 125I-MK 351A binding correlates quantitatively with ACE activity in lung homogenates and isolated, perfused lungs. Lung internal surface area was estimated by measuring the mean alveolar diameter of 5 micron
hematoxylin and
eosin sections from lungs fixed in inflation (25 cmH2O transpulmonary pressure).
Hypoxia adaptation per se had no effect on 125I-MK 351A binding or estimated alveolar surface area, while
hyperoxia exposure caused a significant decrease in both 125I-MK 351A binding and alveolar surface area. These
hyperoxia-induced decreases were prevented partially by
hypoxia adaptation, indicating a protective effect on both ACE content and surface area. 125I-MK 351A binding in isolated perfused lungs changed in parallel with histologically estimated surface area. These results indicate that
hypoxia preadaptation minimizes the
oxygen-induced decrease in lung microvascular ACE content.