Aizawa H, Chung K F, Leikauf G D, Ueki I, Bethel R A, O'Byrne P M, Hirose T, Nadel J A
J Appl Physiol (1985). 1985 Dec;59(6):1918-23. doi: 10.1152/jappl.1985.59.6.1918.
To determine whether thromboxane A2 may be involved in ozone (O3)-induced airway hyperresponsiveness, we studied the effect of a thromboxane synthase inhibitor (OKY-046, 100 micrograms X kg-1 X min-1 iv) in five dogs exposed to O3. Airway responsiveness was assessed by determining the provocative concentration of acetylcholine aerosol that increased total pulmonary resistance by 5 cmH2O X l-1 X s. O3 (3 ppm) increased airway responsiveness as demonstrated by a decrease in acetylcholine provocative concentration from 2.42 (geometric SEM = 1.64) to 0.14 mg/ml (geometric SEM = 1.30). OKY-046 significantly inhibited this effect without altering pre-O3 responsiveness or the O3-induced increase in neutrophils and airway epithelial cells in bronchoalveolar lavage fluid. To further examine the role of thromboxane A2, we studied the effect of a thromboxane A2 mimetic, U-46619, on airway responsiveness in five additional dogs. U-46619 in subthreshold doses (i.e., insufficient to increase base-line pulmonary resistance) caused a fourfold increase in airway responsiveness to acetylcholine. Subthreshold doses of histamine had no effect. These results suggest that thromboxane A2 may be an important mediator of O3-induced airway hyperresponsiveness.
为了确定血栓素A2是否可能参与臭氧（O3）诱导的气道高反应性，我们研究了血栓素合酶抑制剂（OKY - 046，100微克×千克-1×分钟-1静脉注射）对五只暴露于O3的犬的影响。通过测定使总肺阻力增加5厘米水柱×升-1×秒的乙酰胆碱气雾剂激发浓度来评估气道反应性。O3（3 ppm）增加了气道反应性，表现为乙酰胆碱激发浓度从2.42（几何标准误=1.64）降至0.14毫克/毫升（几何标准误=1.30）。OKY - 046显著抑制了这种作用，而不改变O3暴露前的反应性或O3诱导的支气管肺泡灌洗液中中性粒细胞和气道上皮细胞的增加。为了进一步研究血栓素A2的作用，我们研究了血栓素A2模拟物U - 46619对另外五只犬气道反应性的影响。亚阈值剂量的U - 46619（即不足以增加基线肺阻力）使气道对乙酰胆碱的反应性增加了四倍。亚阈值剂量的组胺则没有作用。这些结果表明，血栓素A2可能是O3诱导的气道高反应性的重要介质。
