DIRECT AND INDIRECT EFFECTS OF LEUKOTRIENE-D4 ON THE PULMONARY AND SYSTEMIC CIRCULATIONS
DIRECT AND INDIRECT EFFECTS OF LEUKOTRIENE-D4 ON THE PULMONARY AND SYSTEMIC CIRCULATIONS
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DOI：
10.1164/arrd.1985.131.4.554
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发表时间：
1985-01-01
期刊：
影响因子：
--
通讯作者：
YERGER, L
中科院分区：
文献类型：
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作者：
AHMED, T;MARCHETTE, B;YERGER, L
在6只清醒绵羊上研究了白三烯D4（LTD 4）的直接（血管白三烯受体刺激）和间接（环氧合酶代谢产物的产生）血流动力学效应。测定肺动脉、肺动脉楔嵌、体循环动脉压和心输出量。根据这些参数，在将LTD 4快速注射到肺动脉之前和之后立即计算肺血管阻力（PVR）和全身血管阻力（SVR）。 注射0.1 μ g/kg LTD 4使平均PVR增加至基线的421%（P < 0.001）。它对SVR产生双相效应，在初始下降18%（P < 0.05）后，增加到基线的143%（P < 0.05）。PVR和SVR均在10分钟内恢复到基线。当LTD 4的剂量增加到0.5 μ g/kg时获得相同的结果。随着LTD 4剂量增加（0.025 μ g/kg-0.5 μ g/kg）的剂量-反应曲线显示，最大效果的最佳剂量为0.1 μ g/kg。LTD 4（0.1 μ g/kg）对肺循环的作用被SRS-A拮抗剂FPL-57231以及吲哚美辛完全阻断。在体循环中，FPL-57231阻断了LTD 4对SVR的双相作用，而吲哚美辛阻止了平均SVR的初始降低而没有减弱随后的增加（基线的135%，P < 0.05）。LTD 4有直接和间接的血液动力学效应：全身血管收缩反应与血管白三烯受体刺激直接相关，而环氧合酶途径产物的激活负责肺血管收缩和全身降压反应。
Direct (vascular leukotriene receptor stimulation) and indirect (generation of cyclooxygenase metabolites) hemodynamic effects of leukotriene D4 (LTD4) were investigated in 6 conscious sheep. Pulmonary artery, pulmonary arterial wedge, systemic arterial pressures and cardiac output were measured. From these parameters, pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) were calculated before and immediately after a rapid injection of LTD4 into the pulmonary artery. Injection of 0.1 .mu.g/kg of LTD4 increased mean PVR to 421% of baseline (P < 0.001). It produced a biphasic effect on SVR that, after an initial decrease of 18% (P < 0.05), increased to 143% of baseline (P < 0.05). Both PVR and SVR returned to baseline within 10 min. The same results were obtained when the dose of LTD4 was increased to 0.5 .mu.g/kg. Dose-response curves with increasing doses of LTD4 (0.025 .mu.g/kg-0.5 .mu.g/kg) revealed that the optimal dosage for maximal effect was 0.1 .mu.g/kg. The effects of LTD4 (0.1 .mu.g/kg) on the pulmonary circulation were completely blocked by the SRS-A antagonist, FPL-57231, as well as by indomethacin. In the systemic circulation, FPL-57231 blocked the biphasic effects of LTD4, on SVR, whereas indomethacin prevented the initial decrease without attenuating the subsequent increase in mean SVR (135% of baseline, P < 0.05). There are direct and indirect hemodynamic effects of LTD4: the systemic vasoconstrictor response is directly related to vascular leukotriene receptor stimulation, whereas activation of cyclooxygenase pathway products is responsible for the pulmonary vasoconstrictor and systemic depressor responses.