[Effect of BAY u3405-thromboxane A2 receptor antagonist, on biphasic airway responses induced by platelet-activating factor in actively sensitized guinea pigs].

Our previous study in activity sensitized guinea pigs demonstrated an LAR-like increase in respiratory resistance (Rrs) at 3 to 9 hr after PAF inhalation. The result suggested possible involvement of the priming effect of active sensitization and PAF. Mean while, thromboxane A2 (TXA2) is known to be induced by PAF. The present study investigated the involvement of TXA2 in the guinea pig LAR model with a new TXA2 receptor antagonist, BAY u3405. One hr after BAY u3405 administration to guinea pigs sensitized by ovalbumin, the Rrs following inhalation of PAF was subsequently determined. Infiltration of inflammatory cells in the airway tissue 9 hr after PAF inhalation was also observed. While a re-increase in Rrs was found in all the cases in the control group, the re-increase in Rrs was inhibited significantly in the BAY u3405 administration group, 4 to 9 hr after PAF inhalation. The numbers of eosinophils and lymphocytes in the airway tissue were significantly decreased in the BAY u3405 administration group, as compared with the control group. From these results, the possibility is suggested that TXA2 and its direct effect on the airway and the migration-enhancing effect on eosinophils and T lymphocytes, as well as PFA, are involved in the development of LAR by PAF.