Hypoxia-induced oxygen tolerance: maintenance of endothelial metabolic function.
Hypoxia (10%-12% O2) preadaptation for 4-7 days effectively protects rats from oxygen toxicity. The present study was designed to investigate the hypothesis that the lung's microvascular endothelium shares in development of oxygen tolerance and therefore that endothelial metabolic function would be protected from oxygen toxicity by prior adaptation to hypoxia. Since pulmonary oxygen toxicity decreases lung capillary angiotensin converting enzyme (ACE) activity, we assayed converting enzyme active sites in an isolated perfused rat lung preparation as a marker for the development of oxygen toxicity and tolerance. Rats were exposed to air, hypoxia (10% O2 for 4 days), hyperoxia (greater than 95% O2 for 2 days) alone, or hypoxia followed immediately by hyperoxia. Lung vascular ACE content was quantitated by measuring the single pass binding of an iodinated-converting enzyme inhibitor, 125I-MK351A, a derivative of lisinopril. Hypoxia adaptation per se had no effect on ACE content reflected in normal 125I-MK351A binding, whereas hyperoxia exposure caused a significant decrease in lung vascular ACE. Hyperoxia-induced decreases in ACE content were prevented partially by hypoxia adaptation, indicating that ACE content on luminal endothelial surfaces was protected from oxygen toxicity. In isolated perfused lungs 125I-MK351A binding reflects development of oxygen tolerance after hypoxia preadaptation and suggests that lung endothelial metabolic function is protected from oxygen toxicity.
Jackson
R M
RM
Birmingham VA Medical Center, Alabama 35233.
Ann
H S
HS
Oparil
S
S
D000222:Adaptation, Physiological; D000818:Animals; D004151:Dipeptides / Q000378:metabolism; D004361:Drug Tolerance; D004730:Endothelium, Vascular / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008297:Male; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D004151:Dipeptides; D007457:Iodine Radioisotopes; C042037:L-proline, N2-((1S)-1-carboxy-3-phenylpropyl)-N6-((4-hydroxyphenyl)iminomethyl)-L-lysyl-; D010100:Oxygen