Stephenson A H, Sprague R S, Dahms T E, Lonigro A J
Department of Pharmacology, St. Louis University School of Medicine, Missouri 63104.
J Appl Physiol (1985). 1990 Jul;69(1):345-52. doi: 10.1152/jappl.1990.69.1.345.
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.
血栓素（Tx）被认为可介导佛波醇肉豆蔻酸酯乙酸酯（PMA）诱导的急性肺损伤所致的肺动脉高压。为验证这一假说，在戊巴比妥钠麻醉的雄性杂种犬中，利用PMA诱导急性肺损伤模型评估Tx与肺动脉压之间的关系。静脉注射PMA（20微克/千克，n = 10）60分钟后，全身和肺动脉血中的TxB2较对照组增加了10倍，支气管肺泡灌洗（BAL）液中增加了8倍。与此同时，肺动脉压（Ppa）从14.5±1.0 mmHg升至36.2±3.5 mmHg，肺血管阻力（PVR）从5.1±0.4 mmHg·l-1·min升至25.9±2.9 mmHg·l-1·min。用OKY - 046（10毫克/千克，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浓度升高，但不能防止或减轻Ppa的升高。然而，OKY - 046预处理可减轻但不能防止PMA给药60分钟后PVR的升高。用TxA2/前列腺素H2受体拮抗剂ONO - 3708（10微克·千克-1·分钟-1，静脉注射，n = 7）预处理可防止对Tx受体激动剂1 - 10微克U - 46619推注的升压反应，但不能防止或减轻PMA诱导的Ppa升高。ONO - 3708也可减轻但不能防止PVR的升高。这些结果表明，Tx并不介导PMA诱导的肺动脉高压，但可能在该急性肺损伤模型中增强PVR的升高。
