Lung MK 351A uptake after hypoxia adaptation and subsequent hyperoxia exposure

Robert M. Jackson, Hyung Soo Ann, Suzanne Oparil

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

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 (>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 that125I-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 μm hematoxylin and eosin sections from lungs fixed in inflation (25 cmH2O transpulmonary pressure). Hypoxia adaptation per se had no effect on125I-MK 351A binding or estimated alveolar surface area, while hyperoxia exposure caused a significant decrease in both125I-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.

Original languageEnglish (US)
Pages (from-to)209-219
Number of pages11
JournalLung
Volume166
Issue number1
DOIs
StatePublished - Dec 1 1988
Externally publishedYes

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Keywords

  • Angiotensin-converting enzyme
  • Hyperoxia
  • Hypoxia
  • Lung injury

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology

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