Effects of DP-1904, a thromboxane synthetase inhibitor, on the antigen-induced airway hyperresponsiveness and infiltration of inflammatory cells in guinea-pigs

The effect of DP-1904, a novel thromboxane (TX) synthetase inhibitor, on ai rway hyperresponsiveness was studied in actively sensitized guinea-pigs. Ai rway hyperresponsiveness to intravenous ACh was observed at 3 and 7 h after aerosolized antigen challenge. In the model, a significant correlation bet ween increases of respiratory resistance and microvascular leakage was obse rved, corresponding to the elevation of TXB2 in bronchoalveolar lavage flui d (BALF) in the early phase. DP-1904, at doses of 3 mg/kg or higher given o rally one hour prior to the antigen challenge, inhibited the TXB2 productio n and the development of airway hyperresponsiveness in the early phase. Fur ther, DP-1904 significantly suppressed the accumulation of lymphocytes in B ALF and airway hyperresponsiveness in the late phase, although it only slig htly decreased the mobilization of eosinophils and neutrophils. The results suggest that TXA(2) is possibly involved in the development of airway hype rresponsiveness, and DP-1904 prevented the airway hyperresponsiveness via i nhibition of TXA(2) production and regulation of inflammatory cells.