MONOHYDROXYEICOSATETRAENOIC ACIDS (5-HETE AND 15-HETE) INDUCE PULMONARY VASOCONSTRICTION AND EDEMA
MONOHYDROXYEICOSATETRAENOIC ACIDS (5-HETE AND 15-HETE) INDUCE PULMONARY VASOCONSTRICTION AND EDEMA
复制标题
DOI：
10.1161/01.res.62.4.687
复制
发表时间：
1988-04-01
影响因子：
20.1
通讯作者：
MALIK, AB
中科院分区：
文献类型：
--
作者：
BURHOP, KE;SELIG, WM;MALIK, AB
5-、15-和12-HETE（单羟基二十碳四烯酸）是花生四烯酸脂氧合的产物。我们研究了它们作为肺血管活性和肺水肿的可能介质的作用。肺动脉压(Ppa)、毛细血管压(Pcap)、肺湿重相对于基线的变化(Δwt)和毛细血管滤过系数(Kf)(作为血管渗透性的量度)在用磷酸盐缓冲林格氏白蛋白溶液(PBR)或恒流灌注的肺中静脉内注射每种单-HETE后测定。 稀释的血液。将2μg每种化合物注射到灌注有PBR或稀释血液的肺部肺动脉中没有产生任何效果。然而，在 PBR 灌注的肺中，4 μg 15-HETE 诱导 Ppa、Pcap 和肺湿重增加 (p < 0.05)，这大于 4 μg 5-HETE 后观察到的增加。 5- 和 15-HETE 后 Kf 均增加。通过将灌注液白蛋白浓度从 0.5 g% 增加到 1.5 g%，可以减弱肺血管收缩和水肿反应。相反，12-HETE (4μg)对这些参数没有影响。在血液灌注的肺中，肺血管对所有HETE化合物(4μg)的反应均减弱。在林格氏白蛋白灌注肺和血液灌注肺中，对每种单 HETE 的血流动力学和液体过滤反应的相对大小如下：15-HETE > 5-HETE > 12-HETE。总之，5-和15-HETE 的肺血管收缩和水肿作用的发生与血液形成成分无关。 15-HETE 比 5-HETE 引起更大的肺血管收缩和水肿。 5- 和 15-HETE 均可诱发肺水肿，可能是由于肺血管通透性增加所致。结果表明 5- 和 15-HETE 是有效的肺部炎症介质。
5-, 15-, and 12-HETE (monohydroxyeicosatetraenoic acids) are products of the lipoxygenation of arachidonic acid. We investigated their role as possible mediators of pulmonary vasoactivity and pulmonary edema. Pulmonary artery pressure (Ppa), capillary pressure (Pcap), the change in lung wet weight (.DELTA.wt) from baseline, and capillary filtration coefficient (Kf) (as a measure of vascular permeability) were determined following an intravenous injection of each mono-HETE in lungs perfused at constant flow with either a phosphate-buffered Ringer''s-albumin solution (PBR) or diluted blood. Injection of 2 .mu.g of each compound into the pulmonary artery of lungs perfused with either PBR or diluted blood did not produce any effect. However, in PBR-perfused lungs, 4 .mu.g 15-HETE induced increases in Ppa, Pcap, and lung wet weight (p < 0.05), which were greater than the increases observed after 4 .mu.g 5-HETE. Kf increased following both 5- and 15-HETE. The pulmonary vasoconstrictor and edemagenic responses were attenuated by increasing perfusate albumin concentration from 0.5 to 1.5 g%. In contrast, 12-HETE (4 .mu.g) had no effect on these parameters. In blood-perfused lungs, the pulmonary vascular responses to all HETE compounds (4 .mu.g) were attenuated. In both Ringer''s-albumin-perfused and blood-perfused lungs, the relative magnitude of the hemodynamic and fluid filtration responses to each mono-HETE were as follows: 15-HETE > 5-HETE > 12-HETE. In conclusion, the pulmonary vasoconstrictor and edemagenic effects of 5- and 15-HETE occur independently of blood-formed elements. 15-HETE causes greater pulmonary vasoconstriction and edema than 5-HETE. Both 5- and 15-HETE induce pulmonary edema, probably as a result of increased lung vascular permeability. The results indicate that 5- and 15-HETE are potent pulmonary inflammatory mediators.