Role of thromboxane and prostacyclin in pulmonary vasomotor changes after endotoxin in dogs.
Role of thromboxane and prostacyclin in pulmonary vasomotor changes after endotoxin in dogs.
复制标题
血栓素和前列环素在狗内毒素后肺血管舒缩变化中的作用。
DOI：
10.1172/jci110281
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发表时间：
1981
期刊：
影响因子：
--
通讯作者：
Watkins,WD
中科院分区：
文献类型：
--
作者：
Hales,CA;Sonne,L;Peterson,M;Kong,D;Miller,M;Watkins,WD
环加氧酶抑制剂可防止低剂量内毒素引起的肺血管舒缩变化。因此，我们探讨了两种高血管活性前列腺素类药物——血栓素 A2（一种血管收缩剂）和前列环素（一种血管扩张剂）在内毒素后短暂肺血管收缩和随后肺泡缺氧血管收缩 (AHPV) 丧失中的作用。在狗身上进行了 AHPV 测试，使用双腔气管内插管，允许一侧肺通气氮气作为缺氧挑战，而另一侧肺通气氧气以维持全身氧合。使用静脉内 133Xe 和外部闪烁检测器评估两个肺的灌注的相对分布。采用放射免疫法测定血浆中血栓素和前列环素的稳定代谢物，即血栓素B2和6-酮前列腺素F1α。 15微克/公斤静脉注射内毒素不会引起肺血管阻力 (PVR) 上升，但可以预防 AHPV，因此缺氧肺灌注量最初减少 33% (±2 SEM)，现在仅减少 2% (±1)。血栓素和前列环素的循环水平同时从不可检测水平上升（P<0.01）至380 pg/ml（±40）和360 pg/ml（±130）。 150 μg/kg内毒素导致PVR从4.09毫米汞柱/升/分钟短暂上升至9.00毫米汞柱/升/分钟，与血栓素水平急剧上升至4,460 pg/ml (±1,350)相关(r= 0.89，P< 0.01)，而前列环素水平则不那么明显地上升至550 pg/ml (±400)。另一种血管收缩剂前列腺素 F2α 没有升高。内毒素后 30 分钟，当 PVR 再次达到基线且 AHPV 消失时，血栓素显着下降 (P< 0.01) 至 2,200 pg/ml (±1,100)，而前列环素仍升高至 360 pg/ml (±135)，该水平与 15 μg/kg 内毒素诱导 AHPV 消失时所见的水平相似。吲哚美辛可防止内毒素后血栓素和前列环素的升高以及肺血管舒缩张力的变化。因此，血栓素和前列环素之间复杂的相互作用参与了对低剂量内毒素的肺血管舒缩反应。
Cyclooxygenase inhibitors prevent the pulmonary vasomotor changes in response to low-dose endotoxin. We, therefore, explored the role of two highly vasoactive prostanoids, thromboxane A2, a vasoconstrictor, and prostacyclin, a vasodilator, in the transient pulmonary vasoconstriction and subsequent loss of alveolar hypoxis vasoconstriction (AHPV) that follows endotoxin. AHPV was tested in the dog with a double-lumened endotracheal tube allowing ventilation of one lung with nitrogen as a hypoxic challenge while the other lung was ventilated with oxygen to maintain systemic oxygenation. Relative distribution of perfusion to the two lungs was assessed with intravenous133Xe and external scintillation detectors. The stable metabolites of thromboxane and prostacyclin, i.e., thromboxane B2and 6-keto-prostaglandin F1αwere measured in plasma with radioimmunoassay. 15 μg/kg i.v. of endotoxin induced no rise in pulmonary vascular resistance (PVR), but prevented AHPV so that the initial 33% (±2 SEM) decrease in perfusion to the hypoxic lung became only a 2% (±1) decrease. Circulating levels of thromboxane and prostacyclin concurrently rose (P< 0.01) from nondetectable levels to 380 pg/ml (±40) and 360 pg/ml (±130). 150 μg/kg of endotoxin induced a transient rise in PVR from 4.09 to 9.00 mm Hg/liter per min in association (r= 0.89,P< 0.01) with a sharp rise in thromboxane levels to 4,460 pg/ml (±1,350) whereas prostacyclin levels were elevated less markedly to 550 pg/ml (±400). Prostaglandin F2α, another vasoconstrictor, was not elevated. 30 min after endotoxin when PVR was again base line and AHPV lost, thromboxane fell significantly (P< 0.01) to 2,200 pg/ml (±1,100) whereas prostacyclin remained elevated at 360 pg/ml (±135), a level similar to that seen when 15 μg/kg of endotoxin induced loss of AHPV. Indomethacin prevented the rise in thromboxane and prostacyclin after endotoxin as well as the changes in pulmonary vasomotor tone. Thus, a complex interaction between thromboxane and prostacyclin is involved in the pulmonary vasomotor response to low-dose endotoxin.