Effect of Y-20811, a long-lasting thromboxane A2 synthetase inhibitor, on antigen-induced airway hyperresponsiveness in guinea pigs.

Effect of Y-20811 on airway hyperresponsiveness was studied in sensitized guinea pigs. Airway hyperresponsiveness to acetylcholine (ACh) reached maximum 7 h after antigen challenge in guinea pigs sensitized actively. Y-20811 (0.3-3 mg/kg) administered orally 3 h prior to challenge inhibited this airway hyperresponsiveness in a dose-dependent manner. Y-20811 (3 mg/kg) administered orally 4 h after antigen challenge also decreased the airway hyperresponsiveness. On the other hand, Y-20811 did not affect the bronchoconstriction induced by ACh, serotonin and histamine in nonsensitized guinea pigs. The number of eosinophils in bronchoalveolar lavage fluid in the guinea pig reached the peak 7 h after antigen challenge. Y-20811 had a tendency to decrease the number of total cells, macrophages and eosinophils in a dose-dependent manner. These results suggest that Y-20811 suppress the asthmatic mechanism which causes antigen-induced airway hyperresponsiveness.