Hyman A L, Mathe A A, Leslie C A, Matthews C C, Bennett J T, Spannhake E W, Kadowitz P J
J Pharmacol Exp Ther. 1978 Nov;207(2):388-401.
The effects of bolus injections of arachidonic acid and prostaglandins (PG) E2 and F2a on the pulmonary vascular bed were compared under resting conditions and after alteration in the physiologic state of the lung. Studies were carried out in the vascularly isolated lung lobe of the intact, anesthetized dog under conditions of controlled blood flow. Arachidonic acid, PGE2 and PGF2a increased pulmonary vascular resistance by constricting intrapulmonary veins and arteries in a dose-related manner, as did an analog of the endoperoxide, PGH2, whereas PGI2 dilated the pulmonary vascular bed. The response to arachidonate was associated with a 2- to 3-fold increase in levels of PGE- and PGF-like substances in pulmonary venous blood and was blocked by indomethacin. The effects of arachidonic acid, but not the PGs, were greatly enhanced during perfusion with either dextran or saline and the enhanced response in saline was associated with a 15 to 20-fold increase in levels of PG-like substances in the pulmonary effluent. Responses to arachidonate were not dependent upon the presence of formed elements in blood but were related to perfusate protein concentration. Alveolar hypoxia decreased responses to the precursor while those to PGE2 and PGF2a were enhanced. Responses to the PGs, but not those to arachidonate, were affected by changes in blood pH. Sublethal doses of Escherichic coli endotoxin increased the response to arachidonic acid, but not those to PGE2 and PGF2a. Results of the present study indicate that the effects of bolus injection of arachidonic acid on the pulmonary vascular bed are due mainly to formation of constrictor metabolites which may overshadow the actions of any dilator (PGI2) formed and suggest that metabolism of the precursor is altered by changes in physiologic state.
在静息状态及肺生理状态改变后，比较了一次性注射花生四烯酸、前列腺素（PG）E2和F2α对肺血管床的影响。在完整麻醉犬的血管分离肺叶中，于控制血流的条件下进行研究。花生四烯酸、PGE2和PGF2α通过以剂量相关方式收缩肺内静脉和动脉来增加肺血管阻力，内过氧化物类似物PGH2也是如此，而PGI2则使肺血管床扩张。对花生四烯酸的反应与肺静脉血中PGE样和PGF样物质水平增加2至3倍相关，并被吲哚美辛阻断。在输注右旋糖酐或生理盐水期间，花生四烯酸的作用显著增强，但PGs的作用未增强，且在生理盐水中增强的反应与肺流出物中PG样物质水平增加15至20倍相关。对花生四烯酸的反应不依赖于血液中细胞成分的存在，而是与灌注液蛋白浓度有关。肺泡缺氧降低了对前体的反应，而对PGE2和PGF2α的反应增强。对PGs的反应受血液pH值变化的影响，但对花生四烯酸的反应不受影响。亚致死剂量的大肠杆菌内毒素增加了对花生四烯酸的反应，但未增加对PGE2和PGF2α的反应。本研究结果表明，一次性注射花生四烯酸对肺血管床的影响主要是由于收缩性代谢产物的形成，这可能掩盖了任何形成的扩张剂（PGI2）的作用，并提示前体的代谢因生理状态的改变而改变。
