EFFECT OF THROMBOXANE A(2)-RECEPTOR ANTAGONIST ON BRADYKININ-INDUCED BRONCHOCONSTRICTION IN ASTHMA

The role of the thromboxane A(2) (TxA(2)) receptor in bradykinin-induc ed bronchial responses was investigated in this study by using a selec tive and potent TxA(2)-receptor antagonist BAY u 3405. Eleven asthmati c subjects were randomized to receive 50 mg of BAY u 3405 or matched p lacebo in a crossover and double-blind fashion. Ninety minutes after d osing, serum was taken for drug assay, and subjects underwent provocat ion with bradykinin or prostaglandin D-2 (PGD(2)) to determine bronchi al responsiveness [provocative concentration of agonist required to pr oduce a 20% fall in forced expiratory volume in 1 s from the postdilue nt baseline (PC20)]. Pretreatment with BAY u 3405 caused a twofold dou bling-dilution reduction in bronchial reactivity to PGD(2); the geomet ric mean PC20 values were 0.132 (0.015-0.871) and 0.034 (0.008-0.095) mg/ml, respectively, for active and placebo days (P = 0.001). There wa s, however, no significant difference in PC20 values for bradykinin be tween active and placebo treatment days. We have demonstrated that BAY u 3405 caused a significant inhibition of bronchconstriction induced by inhaled PCTD2 but had no influence on bronchial responsiveness to i nhaled bradykinin. This study suggests therefore that TxA(2) receptors do not play a role in bradykinin-induced bronchoconstriction in asthm a.