ono-nt-126 and Inflammation

Although it is well recognized that beta-blockers can induce bronchoconstriction only in patients with asthma, mechanisms of the bronchoconstriction are not well known. We hypothesize that bronchoconstriction induced by beta-blockers may result from inflammatory mediators released by allergic reactions. In this study, we developed a guinea pig model for propranolol-induced bronchoconstriction (PIB) after antigen inhalation and investigated the effect of specific thromboxane (TXA2) receptor antagonists, S-1452 and ONO NT-126, on PIB in passively sensitized and artificially ventilated guinea pigs to determine whether TXA2 is involved in PIB. Propranolol caused bronchoconstriction with 10 mg/ml of propranolol was inhaled 20 min after antigen challenge. On the other hand, propranolol did not produce bronchoconstriction after antigen provocation in nonsensitized guinea pigs or after saline provocation 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 micrograms/kg injected intravenously 15 min after antigen challenge as well as before antigen challenge reduced PIB in a dose-dependent manner. Bronchoconstriction caused by methacholine did not induce PIB. These results suggest that TXA2 has an important role in the pathophysiology of the PIB that develops after the allergic bronchoconstriction.

Topics: Administration, Inhalation; Analysis of Variance; Animals; Asthma; Bridged Bicyclo Compounds; Bronchial Provocation Tests; Constriction, Pathologic; Disease Models, Animal; Dose-Response Relationship, Drug; Fatty Acids, Monounsaturated; Guinea Pigs; Hypersensitivity; Inflammation; Injections, Intravenous; Male; Methacholine Chloride; Premedication; Propranolol; Receptors, Prostaglandin; Thromboxane A2; Time Factors