title: Early detection of oxygen-induced lung injury in conscious rabbits. Reduced in vivo activity of angiotensin converting enzyme and removal of 5-hydroxytryptamine.
abstract: Changes in lung endothelial metabolic function, determined in vitro, have been proposed as sensitive indexes of hyperoxic lung damage. However, it is unclear whether these changes are also seen in vivo. We studied the possibility, using conscious rabbits in which jugular and carotid catheters had previously been placed under halothane anesthesia. Approximately 24 h later, test animals were exposed to normobaric hyperoxia (96 +/- 2%), while a second group was maintained in room air. Multiple indicator dilution methods were used to study (1) metabolism of 3H-benzoyl-phe-ala-pro (BPAP), a synthetic substrate for angiotensin converting enzyme (ACE), and (2) removal of 14C-5-hydroxytryptamine (5-HT) during a single transpulmonary passage in conscious animals. Determinations were made serially during exposure (room air or hyperoxia) or until death occurred in the oxygen-treated animals. Lungs of air-exposed animals hydrolyzed 81 +/- 2% of injected BPAP (0.1 to 0.15 nmoles) during a single passage. Percent metabolism was unaltered during the next 72 h. However, in test animals, ACE activity, as reflected by BPAP metabolism, was significantly reduced after 16 h of exposure to oxygen (77 +/- 2%, p less than 0.01) and continued to decrease to a nadir of 66 +/- 3% at 40 h. Single-pass lung uptake of 14C-5-HT (77 +/- 2%) was unchanged throughout the 72-h period in air-exposed rabbits. In test animals, 14C-5-HT removal decreased to 65 +/- 4% (p less than 0.01) after 24 h of oxygen exposure; 5-HT removal remained depressed compared with the 0 h control determination for the oxygen group at all subsequent measurement intervals. Light and electron microscopy of lungs from oxygen-exposed rabbits demonstrating reduced 5-HT removal and ACE activity at 24 h revealed normal endothelial and type I cell morphologic features. We conclude that exposure to 100% oxygen produced significant reduction in pulmonary 5-HT removal and BPAP metabolism prior to the onset of morphologic damage.
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes; D003243:Consciousness; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D009842:Oligopeptides / Q000378:metabolism; D010100:Oxygen / Q000506:poisoning*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors; D014316:Tritium
chemical_list: D002250:Carbon Radioisotopes; D009842:Oligopeptides; D014316:Tritium; D012701:Serotonin; C029689:benzoylphenylalanyl-alanyl-proline; D007703:Peptidyl-Dipeptidase A; D010100:Oxygen