Burghuber O C, Strife R, Zirolli J, Mathias M M, Murphy R C, Reeves J T, Voelkel N F
Wien Klin Wochenschr. 1986 Feb 21;98(4):117-9.
Reactive oxygen metabolites cause pulmonary vasoconstriction and activate arachidonic acid metabolism. We proposed that hydrogen peroxide, generated enzymatically in an insolated rat lung model, would cause vasoconstriction which was independent of circulating cells, but dependent on activation of the arachidonic acid cascade. Although hydrogen peroxide caused an increase in lung effluent thromboxane B2 concentration, indomethacin did not inhibit hydrogen peroxide induced vasoconstriction. In order to test the hypothesis that hydrogen peroxide activates the 5-lipoxygenase pathway, lung effluents were analyzed for 5-hydroxy-eicosatetranoic acid (5-HETE) using a sensitive, highly specific mass spectrometer technique. Glucose oxidase increased the 5-HEFE effluent concentrations and this was prevented by U60,257. We therefore conclude that hydrogen peroxide stimulates the 5-lipoxygenase pathway and that substances derived from this pathway are at least in part responsible for the hydrogen peroxide induced vasoconstriction in isolated rat lungs.
活性氧代谢产物可引起肺血管收缩并激活花生四烯酸代谢。我们提出，在孤立大鼠肺模型中酶促产生的过氧化氢会引起血管收缩，这种收缩不依赖于循环细胞，而是依赖于花生四烯酸级联反应的激活。尽管过氧化氢导致肺流出液中血栓素B2浓度升高，但吲哚美辛并未抑制过氧化氢诱导的血管收缩。为了检验过氧化氢激活5-脂氧合酶途径的假说，使用灵敏、高度特异的质谱技术分析肺流出液中的5-羟基二十碳四烯酸（5-HETE）。葡萄糖氧化酶增加了5-HETE流出液浓度，而U60,257可阻止这种增加。因此，我们得出结论，过氧化氢刺激5-脂氧合酶途径，且该途径衍生的物质至少部分负责过氧化氢诱导的孤立大鼠肺血管收缩。
