Modification by betamethasone of the effects of bronchodilator drugs on cholinergic bronchoconstriction in rats

Abstract

Effects of betamethasone (BM), a long-acting glucocorticoid, given alone and in combination with bronchodilator drugs, terbutaline (Ter), theophylline (Theo), or ipratropium bromide (Ipra), were studied on dose-related methacholine (MeCh 2, 3, and 4.5 micrograms i.v.)-induced bronchoconstriction in anaesthetized rats. BM (0.4 or 2 mg kg-1) was given intraperitoneally 24 h before the experiment followed by a similar dose intravenously, 12 min before MeCh challenge. The bronchodilator drugs were given i.v. as acute single doses. BM 0.4 mg kg-1 counteracted significantly MeCh-induced bronchoconstriction without modifying MeCh-induced transient bradycardia and hypotension. BM 2 mg kg-1 failed to improve that response. A time interval of 24 h after pretreatment proved mandatory to produce these effects. Combined treatment with BM 0.4 mg kg-1 + Ter 20 micrograms kg-1 antagonized the MeCh-induced bronchoconstriction in an additive manner at 2 and 3 micrograms of MeCh, but a synergistic interaction was found at the largest MeCh dose. The effects of the other combinations (BM 0.4 mg kg-1 + Theo 20 mg kg-1 and BM 0.4 mg kg-1 + Ipra 0.5 microgram kg-1) on airways failed to exceed the expected sum of the individual drugs. The combination of BM + Ter was selective to the airways only, whereas BM + Theo also counteracted MeCh-induced bradycardia and BM + Ipra counteracted both hypotension and bradycardia. It is concluded that combined treatment with glucocorticoid and beta 2-adrenoceptor agonist may result in a synergistic interaction on severe airway obstruction without significant influence on cardiovascular system.