Inhibitory effect of inhalation of a thromboxane synthetase inhibitor on bronchoconstriction induced by aerosolized leukotriene C4 and thromboxane A2 analogue in anesthetized guinea pigs

Effect of aerosol administration of a thromboxane synthetase inhibitor (OKY-046) on bronchoconstriction induced by aerosol leukotriene C4, histamine and a thromboxane A2 analogue (STA2) was studied in anesthetized, artificially ventilated guinea pigs in order to evaluate the effectiveness of inhalation of OKY-046 on an unfavorable mechanism of secondary release of thromboxane A2. 0.01-1.0 micrograms/ml leukotriene C4, 25-400 micrograms/ml histamine and 0.033-1.0 micrograms/ml STA2 inhaled from an ultrasonic nebulizer developed for small animals caused a dose-dependent increase of pressure at the airway opening (Pao), which is considered to be an index representing bronchial response. Pretreatment of the animals with aerosol OKY-046 (0.035 and 0.35 mg/animal) significantly reduced the airway responses produced by inhalation of leukotriene C4 and STA2, in a dose-dependent manner, while the pretreatment did not affect the histamine dose-response curve. These findings suggest that aerosol leukotriene C4 and STA2 activate thromboxane synthesis in the airway, and inhalation of OKY-046 may be useful for preventing the secondary release of thromboxane A2, which is an unfavorable mechanism in asthma.