{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T04:10:59Z","timestamp":1774930259077,"version":"3.50.1"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[1988,7,1]],"date-time":"1988-07-01T00:00:00Z","timestamp":583718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1988,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Despite the potential utility of endothelial metabolic substrates for the early clinical detection of acute lung injury, the relationship between lung capillary injury and pulmonary endothelial metabolic function remains incompletely understood. Previous studies have shown that lung capillaries are damaged by oxygen toxicity in the sheep; however, metabolic functions of the pulmonary endothelium have not been examined in this otherwise well-characterized animal model of lung injury. Therefore, we studied the activity of pulmonary endothelial angiotensin-converting enzyme (ACE) in five unanesthetized adult sheep that breathed 100% O2 via tracheostomy for 3 days and in four other sheep that breathed compressed air. In contrast to the sheep that breathed air, the sheep that breathed O2 developed substantial arterial hypoxemia and hypercapnia, an increased alveolar-to-arterial O2 gradient and a slight respiratory acidosis. Morphological examination of lungs from sheep that breathed O2 revealed a multifocal distribution of injury, including interstitial edema, capillary endothelial damage, and alveolar epithelial damage. Indicator-dilution methods were used to assess first-pass pulmonary metabolism of the ACE substrate [3H]Benzoyl-Phe-Ala-Pro (BPAP) and the apparent kinetics (K \u00a0M and Vmax) of ACE activity. Pulmonary metabolism of BPAP exhibited saturability, was reduced by an ACE inhibitor (enalaprit), and did not result from the activity of circulating plasma ACE. There was no difference between the 2 groups of sheep in the percent metabolism of either 0.1 \u00b5mol BPAP\/kg or 1.0 \u00b5mol BPAP\/kg or in the K \u00a0M of BPAP metabolism. In both groups, the Vmax and Vmax\/K \u00a0M decreased as a result of reductions in cardiac output and volume of distribution. To further examine pulmonary endothelial ACE activity, we assessed the first-pass pulmonary uptake of an ACE inhibitor, [14C]captopril, in 4 additional sheep that breathed O2; [14C]captopril uptake remained unchanged from control. We conclude that in sheep 3 days of O2 breathing causes moderately severe gas exchange abnormalities and capillary damage without impairing pulmonary endothelial ACE activity.<\/jats:p>","DOI":"10.1164\/ajrccm\/138.1.160","type":"journal-article","created":{"date-parts":[[2011,7,20]],"date-time":"2011-07-20T05:44:11Z","timestamp":1311140651000},"page":"160-166","source":"Crossref","is-referenced-by-count":3,"title":["Pulmonary Angiotensin-converting Enzyme Activity in the Oxygen-toxic Sheep"],"prefix":"10.1093","volume":"138","author":[{"given":"Ralph E.","family":"Howell","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John H.","family":"Hansen-Flaschen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric B.","family":"Wheeldon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1988,7,1]]},"reference":[{"key":"p_11","first-page":"424","volume":"130","year":"1984","journal-title":"Respir Dis"},{"key":"p_15","first-page":"185","year":"1981","journal-title":"Physiol Scand"},{"key":"p_18","unstructured":"physiological effects. 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