The effect of leukotriene C4/D4 receptor antagonist (ONO-1078) and thromboxane A2 synthetase inhibitor (OKY-046) on airway hyperresponsiveness induced by ozone exposure in guinea pigs

Abstract

To clarify the mechanisms of ozone-induced airway hyperresponsiveness, we studied the effect of leukotriene C4/D4 receptor antagonist (ONO-1078) and thromboxane A2 synthetase inhibitor (OKY-046) on airway hyperresponsiveness induced by ozone exposure in guinea pigs. Airway responsiveness to inhaled methacholine was determined in artificially ventilated guinea pigs using a modification of the Konzett-Rössler technique. After the methacholine challenge, bronchoalveolar lavage (BAL) was performed. After 1 hour following ozone exposure (2.9 ppm, 30 min), airway responsiveness increased significantly. There was no cellular change in the bronchoalveolar lavage fluid (BALF). Pretreatment with ONO-1078 (30 mg/kg, i.p.) or OKY-046 (20 mg/kg, i.p.) caused no effect on airway responsiveness before ozone exposure, and inhibited the increase of airway responsiveness induced by ozone exposure. These results suggest that leukotriene and thromboxane play an important role in the development of airway hyperresponsiveness induced by ozone exposure in guinea pigs.