Hyperoxia decreases cyclooxygenase activity in endothelial cells.
We examined the effect of hyperoxia on arachidonic acid (AA) metabolism in bovine carotid artery endothelial cells (CAEC) and pulmonary artery endothelial cells (PAEC). Confluent monolayers were exposed to hyperoxic gases (95% O2 or 60% O2) from 12-72 h. Control cells were incubated under normoxic condition (air-5% CO2). After exposure of the cells to normoxic or hyperoxic conditions, prostaglandin (PG) synthesis activity was analyzed in cell homogenates using thin layer chromatography; release of 6-keto-PGF1 alpha, a stable metabolite of PGI2, into the culture medium was measured using a radioimmunoassay. The major metabolites formed from exogenously supplied 14C-AA were 6-keto-PGF1 alpha and a small amount of PGE2. Hyperoxia (95% O2) decreased the synthesis of these cyclooxygenase products beginning at 24 h; moderate hyperoxia (60% O2) had no such effect. There was no significant difference between CAEC and PAEC with respect to the depletion effect of hyperoxia. After 72 h of exposure to 95% O2, endothelial injury was observed in CAEC but not in PAEC. We conclude that hyperoxia decreases cyclooxygenase activity in endothelial cells, and that this decrease is dependent on the severity of the hyperoxia. In addition, CAEC are more susceptible to hyperoxia-induced injury than PAEC. The depletion of cyclooxygenase activity and the resultant effect on PGI2 and PGE2 production may be a factor in the development of hyperoxia-induced endothelial injury.
Ishii
Y
Y
Department of Pulmonary Medicine, Jichi Medical School, Tochigi, Japan.
Morita
I
I
Murota
S
S
Kitamura
S
S
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002417:Cattle; D002452:Cell Count; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology* / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis; D011460:Prostaglandins F / Q000378:metabolism
D011453:Prostaglandins; D011460:Prostaglandins F; D016718:Arachidonic Acid; D007770:L-Lactate Dehydrogenase; D011451:Prostaglandin-Endoperoxide Synthases; D010100:Oxygen; C100006:prostaglandin F1