Thromboxane does not mediate pulmonary hypertension in phorbol ester-induced acute lung injury in dogs.
Thromboxane does not mediate pulmonary hypertension in phorbol ester-induced acute lung injury in dogs.
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血栓烷不会介导佛波酯引起的狗急性肺损伤的肺动脉高压。
DOI：
10.1152/jappl.1990.69.1.345
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Lonigro,AJ
中科院分区：
文献类型：
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作者：
Stephenson,AH;Sprague,RS;Dahms,TE;Lonigro,AJ
血栓烷（Tx）被认为可以介导佛波醇肉豆蔻酸酯乙酸酯（PMA）引起的急性肺损伤的肺动脉高压。为了检验这一假设，在戊巴比妥钠麻醉的雄性杂种犬中用 PMA 诱导的急性肺损伤模型中评估了 Tx 与肺动脉压之间的关系。给予 PMA（20 微克/千克，静脉注射，n = 10）60 分钟后，全身和肺动脉血中的 TxB2 较对照增加 10 倍，支气管肺泡灌洗 (BAL) 液中的 TxB2 较对照增加 8 倍。同时，肺动脉压(Ppa)从14.5+/-1.0增加到36.2+/-3.5mmHg，肺血管阻力(PVR)从5.1+/-0.4增加到25.9+/-2.9mmHg.l-1.min。用 OKY-046（10 mg/kg 静脉注射，n = 6）抑制 Tx 合酶可防止 PMA 诱导的血液和 BAL 液中 Tx 浓度的增加，但不能防止或减弱 Ppa 的增加。然而，OKY-046 预处理确实减弱但不能阻止 PMA 给药后 60 分钟 PVR 的增加。使用 TxA2/前列腺素 H2 受体拮抗剂 ONO-3708（10 微克.kg-1.min-1 静脉注射，n = 7）进行预处理可防止推注 1-10 微克 U-46619（一种 Tx 受体激动剂）产生的升压反应，但不能防止或减弱 PMA 诱导的 Ppa 增加。 ONO-3708 也减弱了 PVR，但没有阻止 PVR 的增加。这些结果表明，Tx 不会介导 PMA 诱导的肺动脉高压，但可能会增强这种急性肺损伤模型中 PVR 的增加。
Thromboxane (Tx) has been suggested to mediate the pulmonary hypertension of phorbol myristate acetate- (PMA) induced acute lung injury. To test this hypothesis, the relationship between Tx and pulmonary arterial pressure was evaluated in a model of acute lung injury induced with PMA in pentobarbital sodium-anesthetized male mongrel dogs. Sixty minutes after administration of PMA (20 micrograms/kg iv, n = 10), TxB2 increased 10-fold from control in both systemic and pulmonary arterial blood and 8-fold in bronchoalveolar lavage (BAL) fluid. Concomitantly, pulmonary arterial pressure (Ppa) increased from 14.5 +/- 1.0 to 36.2 +/- 3.5 mmHg, and pulmonary vascular resistance (PVR) increased from 5.1 +/- 0.4 to 25.9 +/- 2.9 mmHg.l-1.min. Inhibition of Tx synthase with OKY-046 (10 mg/kg iv, n = 6) prevented the PMA-induced increase in Tx concentrations in blood and BAL fluid but did not prevent or attenuate the increase in Ppa. OKY-046 pretreatment did, however, attenuate but not prevent the increase in PVR 60 min after PMA administration. Pretreatment with the TxA2/prostaglandin H2 receptor antagonist ONO-3708 (10 micrograms.kg-1.min-1 iv, n = 7) prevented the pressor response to bolus injections of 1-10 micrograms U-46619, a Tx receptor agonist, but did not prevent or attenuate the PMA-induced increase in Ppa. ONO-3708 also attenuated but did not prevent the increase in PVR. These results suggest that Tx does not mediate the PMA-induced pulmonary hypertension but may augment the increases in PVR in this model of acute lung injury.