INVOLVEMENT OF THROMBOXANE A(2) IN PROPRANOLOL-INDUCED BRONCHOCONSTRICTION AFTER ALLERGIC BRONCHOCONSTRICTION IN GUINEA-PIGS

Although it is well recognized that beta-blockers can induce bronchoco nstriction only in patients with asthma, mechanisms of the bronchocons triction are not well known. We hypothesize that bronchoconstriction i nduced by beta-blockers may result from inflammatory mediators release d by allergic reactions. In this study, we developed a guinea pig mode l for propranolol-induced bronchoconstriction (PIB) after antigen inha lation and investigated the effect of specific thromboxane (TXA(2)) re ceptor antagonists, S-1452 and ONO NT-126, on PIB in passively sensiti zed and artificially ventilated guinea pigs to determine whether TXA(2 ) is involved in PIB. Propranolol caused bronchoconstriction when 10 m g/ml of propranolol was inhaled 20 min after antigen challenge. On the other hand, propranolol did not produce bronchoconstriction after ant igen provocation in nonsensitized guinea pigs or after saline provocat ion in sensitized animals. Pretreatment of the animals with S-1452 in doses of 0.01 and 0.1 mg/kg and ONO NT-126 in doses of 1.0 and 10 mu g /kg injected intravenously 15 min after antigen challenge as well as b efore antigen challenge reduced PIB in a dose-dependent manner. Bronch oconstriction caused by methacholine did not induce PIB. These results suggest that TXA(2) has an important role in the pathophysiology of t he PIB that develops after the allergic bronchoconstriction.