Madden M C, Vender R L, Friedman M
Prostaglandins. 1986 Jun;31(6):1049-62. doi: 10.1016/0090-6980(86)90208-x.
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.
将培养的牛肺动脉内皮细胞暴露于不同程度的低氧环境（10%或0%氧气）4小时，会导致内皮前列环素合成受到显著的剂量依赖性抑制（在10%和0%氧气水平下分别为51%和98%，与21%氧气暴露值相比，p小于0.05）。低氧环境并未改变细胞池中3H - 花生四烯酸的释放。部分细胞在暴露后立即用花生四烯酸（20微摩尔，5分钟）或PGH2（4微摩尔，2分钟）进行孵育。暴露于0%氧气而非10%氧气的内皮细胞，在添加花生四烯酸（为21%氧气暴露值的25±5%，n = 6，p小于0.01）或PGH2（为21%氧气暴露值的31±3%，n = 6，p小于0.05）后，产生的前列环素显著减少。这些结果表明，低氧在10%氧气水平下抑制环氧化酶，在0%氧气暴露水平下同时抑制环氧化酶和前列环素合成酶。将主动脉内皮细胞暴露于低氧环境，在0%暴露水平下会导致前列环素产生受到44%的抑制。在暴露于低氧环境的肺血管平滑肌细胞中，未发现前列环素产生有显著改变。这些数据表明，在暴露于低氧环境的肺中所报道的前列环素产生增加，并非由于低氧对肺循环中主要前列环素产生细胞的直接作用。
