Littner M R, Kazmi G M, Lott F D
Prostaglandins Leukot Med. 1984 Jul;15(1):53-68. doi: 10.1016/0262-1746(84)90056-8.
We examined the hypothesis that arachidonic acid can lead to pulmonary edema, increased pulmonary vascular permeability, and increased pulmonary vascular resistance (PVR) in an isolated dog lung. The lung was perfused with a dextran-salt solution to remove blood elements. Compared to controls, 20 mg/min sodium arachidonate into the pulmonary circulation led to edema and to an increase in a permeability and surface area index (PSI%), PVR, and cyclooxygenase (i.e. prostaglandin) production as measured by 6-keto-PGF1 alpha, TXB2 and PGF2 alpha. With 20 mg/min arachidonate, indomethacin inhibited the increase in cyclooxygenase production, reduced the increase in PVR and increased the edema and PSI%. Indomethacin, alone, did not produce edema or an increase in PSI% or PVR. Lower doses of arachidonate (0.1 to 5 mg/min) led to increasing cyclooxygenase production without obvious edema or an increase in PSI% or PVR. We conclude: 1) arachidonate can lead to pulmonary edema and an increase in PVR, and may lead to an increase in pulmonary vascular permeability; these effects of arachidonate do not require normal numbers of circulating blood elements; 2) arachidonate appears to contribute to pulmonary edema and increased PSI% by a noncyclooxygenase effect since inhibition of cyclooxygenase production did not prevent, and lower doses of cyclooxygenase production did not produce edema or an increase in PSI%; 3) the increase in PVR appeared to have a cyclooxygenase component since inhibition of cyclooxygenase production reduced the increase, and 4) indomethacin can increase the magnitude of edema and PSI% from arachidonate by an undefined mechanism.
花生四烯酸可导致离体犬肺出现肺水肿、肺血管通透性增加以及肺血管阻力（PVR）升高。用葡聚糖 - 盐溶液灌注肺以去除血液成分。与对照组相比，向肺循环中注入20mg/min的花生四烯酸钠可导致肺水肿，并使通透性和表面积指数（PSI%）、PVR以及通过6 - 酮 - PGF1α、TXB2和PGF2α测量的环氧化酶（即前列腺素）生成增加。注入20mg/min花生四烯酸时，吲哚美辛抑制环氧化酶生成增加，降低PVR升高幅度，并增加肺水肿和PSI%。单独使用吲哚美辛不会产生肺水肿或使PSI%或PVR升高。较低剂量的花生四烯酸（0.1至5mg/min）导致环氧化酶生成增加，但无明显肺水肿或PSI%或PVR升高。我们得出以下结论：1）花生四烯酸可导致肺水肿和PVR升高，并可能导致肺血管通透性增加；花生四烯酸的这些作用不需要正常数量的循环血液成分；2）花生四烯酸似乎通过非环氧化酶效应导致肺水肿和PSI%增加，因为抑制环氧化酶生成并不能预防，且较低剂量的环氧化酶生成也不会产生水肿或使PSI%增加；3）PVR升高似乎有环氧化酶成分，因为抑制环氧化酶生成可降低升高幅度；4）吲哚美辛可通过一种不明机制增加花生四烯酸所致的水肿程度和PSI%。
