Olson N C, Kruse-Elliott K T, Johnson L W
Department of Anatomy, Physiological Sciences and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh 27606.
Prostaglandins Leukot Essent Fatty Acids. 1993 Aug;49(2):549-59. doi: 10.1016/0952-3278(93)90160-x.
We hypothesized that 5-lipoxygenase and cyclooxygenase products might be mediators of cardiopulmonary and systemic vascular effects induced by a 4 h continuous infusion of platelet-activating factor (PAF, 10 ng/kg/min) in anesthetized pigs. Indomethacin (cyclooxygenase inhibitor) potentiated and CGS 8515 (5-lipoxygenase inhibitor) attenuated PAF-induced increases in total peripheral resistance (TPR) from 2.5 to 4 h. However, the 5-lipoxygenase inhibitor failed to modify pulmonary vasoconstriction and hypertension caused by PAF. Except for a delay in onset (approximately 44 s) and rate of development of pulmonary hypertension during the initial 10 min of PAF infusion, the pulmonary hemodynamic changes were also not attenuated by indomethacin. On the other hand, at 4 h, the PAF-induced pulmonary hypertension and systemic vasoconstriction were completely or partially reversed, respectively, by WEB 2086 (PAF receptor antagonist). The PAF-induced increases in plasma thromboxane B2 (TXB2) were blocked by indomethacin but not by CGS 8515, and at 4 h the 5-lipoxygenase inhibitor potentiated the levels of TXB2 in pigs treated with PAF. The plasma concentrations of 6-keto-PGF1 alpha and leukotriene B4 (LTB4) were not modified by PAF or CGS 8515 + PAF. We conclude that PAF-induced increases in TPR (2.5-4 h) are potentiated by indomethacin and are dependent on 5-lipoxygenase products other than LTB4. Although the early pulmonary vascular response (< 10 min) to PAF is dependent on cyclooxygenase products, the sustained response (after 10 min) cannot be explained by either 5-lipoxygenase or cyclooxygenase products but may be mediated directly by PAF receptors.
我们假设，在麻醉猪中，5-脂氧合酶和环氧化酶产物可能是由连续4小时输注血小板活化因子（PAF，10纳克/千克/分钟）诱导的心肺和全身血管效应的介质。吲哚美辛（环氧化酶抑制剂）增强了，而CGS 8515（5-脂氧合酶抑制剂）减弱了PAF在2.5至4小时内诱导的总外周阻力（TPR）增加。然而，5-脂氧合酶抑制剂未能改变PAF引起的肺血管收缩和高血压。除了在PAF输注最初10分钟内肺动脉高压的发作延迟（约44秒）和发展速度外，吲哚美辛也未减弱肺血流动力学变化。另一方面，在4小时时，WEB 2086（PAF受体拮抗剂）分别完全或部分逆转了PAF诱导的肺动脉高压和全身血管收缩。PAF诱导的血浆血栓素B2（TXB2）增加被吲哚美辛阻断，但未被CGS 8515阻断，并且在4小时时，5-脂氧合酶抑制剂增强了PAF处理猪的TXB水平。PAF或CGS 8515 + PAF未改变血浆6-酮-PGF1α和白三烯B4（LTB4）的浓度。我们得出结论，吲哚美辛增强了PAF诱导的TPR增加（2.5至4小时），并且该增加依赖于除LTB4之外的5-脂氧合酶产物。尽管对PAF的早期肺血管反应（<10分钟）依赖于环氧化酶产物，但持续反应（10分钟后）不能用5-脂氧合酶或环氧化酶产物来解释，而可能直接由PAF受体介导。
