Seeger W, Wolf H, Stähler G, Neuhof H, Róka L
Prostaglandins. 1982 Feb;23(2):157-73. doi: 10.1016/0090-6980(82)90043-0.
Liberation and metabolism of arachidonic acid may be the common final pathway of different stimuli on the pulmonary vascular bed. In a model of isolated, ventilated rabbit lungs, perfused with Krebs Henseleit albumin buffer in a recirculating system, changes of pulmonary vascular resistance and of vascular permeability are monitored continuously. The addition of free arachidonic acid or of the Ca-ionophore A 23187 to the perfusion fluid consistently evokes a biphasic increase in vascular resistance as well as an initially reversible increase in vascular permeability, followed by pulmonary edema. Both phases of increased vascular resistance are completely suppressed by inhibition of the cyclooxygenase, decreased to a large degree by inhibitors of thromboxane synthetase, and markedly augmented by short preincubation of arachidonic acid with ram seminal vesicular microsomes and by sulfhydryl reagents. The increased pulmonary vascular permeability is augmented by inhibition of cyclooxygenase and reduced by simultaneous lipoxygenase inhibition. Antagonists of histamine, serotonin and sympathic or parasympathic activity do not have any influence. PG F2alpha., TxB2, PG E2 and PG I2 alter the pulmonary vascular resistance, but do not increase vascular permeability. In conclusion, increased availability of free arachidonic acid evokes a rise in pulmonary vascular resistance, which can be ascribed to cyclooxygenase products, especially to thromboxane, and causes a rise in vascular permeability which can be ascribed to lipoxygenase products. The findings may be related to acute pulmonary lesions with increase in vascular resistance and with vascular leakage.
花生四烯酸的释放和代谢可能是不同刺激作用于肺血管床的共同最终途径。在一个离体通气兔肺模型中，在循环系统中用 Krebs Henseleit 白蛋白缓冲液灌注，连续监测肺血管阻力和血管通透性的变化。向灌注液中添加游离花生四烯酸或钙离子载体 A 23187 会持续引起血管阻力的双相增加以及血管通透性最初可逆的增加，随后出现肺水肿。血管阻力增加的两个阶段都可通过抑制环氧化酶而完全被抑制，在很大程度上被血栓素合成酶抑制剂降低，并通过花生四烯酸与公羊精囊微粒体的短暂预孵育以及巯基试剂而显著增强。肺血管通透性增加通过抑制环氧化酶而增强，通过同时抑制脂氧合酶而降低。组胺、5-羟色胺以及交感或副交感活性的拮抗剂均无任何影响。前列腺素 F2α、血栓素 B2、前列腺素 E2 和前列腺素 I2 可改变肺血管阻力，但不会增加血管通透性。总之，游离花生四烯酸可用性增加会引起肺血管阻力升高，这可归因于环氧化酶产物，尤其是血栓素，并且会导致血管通透性升高，这可归因于脂氧合酶产物。这些发现可能与伴有血管阻力增加和血管渗漏的急性肺部病变有关。
