Effect of hypoxia on prostacyclin production in cultured pulmonary artery endothelium.
Exposure of cultured bovine pulmonary artery endothelial cells to varying levels of hypoxia (10% or 0% O2) for 4 hours resulted in a significant dose-dependent inhibition in endothelial prostacyclin synthesis (51% and 98%, at the 10% and 0% O2 levels respectively, p less than 0.05, compared to 21% O2 exposure values). Release of 3H-arachidonic acid from cellular pools was not altered by hypoxia. Some of the cells were incubated with arachidonic acid (20 microM for 5 min) or PGH2 (4 microM for 2 min) immediately after exposure. Endothelium exposed to 0% O2, but not to 10% O2, produced significantly less prostacyclin after addition of either arachidonic acid (25 +/- 5% of 21% O2 exposure values, n = 6, p less than 0.01) or PGH2 (31 +/- 3% of 21% O2 exposure values, n = 6, p less than 0.05). These results suggest that hypoxia inhibits cyclooxygenase at the 10% O2 level and both cyclooxygenase and prostacyclin synthetase enzymes at the 0% O2 exposure levels. Exposure of aortic endothelial cells resulted in a 44% inhibition of prostacyclin at the 0% exposure level. No significant alteration in prostacyclin production was found in pulmonary vascular smooth muscle cells exposed to hypoxia. These data suggest that the increased prostacyclin production reported in lungs exposed to hypoxia is not due to a direct effect of hypoxia on the main prostacyclin producing cells of the pulmonary circulation.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism*; D000860:Hypoxia / Q000503:physiopathology*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013929:Thromboxane B2 / Q000378:metabolism
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D010100:Oxygen