Reversing Effect of Anti-Asthmatic Drugs on Bronchoconstriction Induced by Antigen Challenge and Histamine in Anesthetized Guinea Pigs.

Abstract

We performed an in vivo evaluation of bronchodilation using a model of antigen-induced bronchoconstriction in anesthetized guinea pigs pretreated with indomethacin, pyrilamine and propranolol, and the results were compared with those for the histamine-induced response. Test drugs were administered intravenously when the antigen or histamine response reached its peak. Leukotriene (LT) D4 antagonists, FPL55712 and LY171883, gradually reduced the antigen-induced response, whereas the lipoxygenase inhibitor phenidone had no such effect. The bronchodilator theophylline rapidly reduced the antigen-induced response, and the adenylate cyclase activator forskolin had a similar effect. The following drugs also had no effect: nifedipine (calcium-channel antagonist), cromakalim (potassium-channel opener), amlexanox and disodium cromoglycate: DSCG (anti-allergic drugs), OKY-046 (thromboxane A2 synthetase inhibitor), and dapsone (anti-inflammatory drug). Theophylline, the beta-adrenoceptor agonist salbutamol and the histamine H1-blocker pyrilamine had only a small reversing effect on histamine-induced bronchoconstriction. These results suggest that antigen-, but not histamine-, induced bronchoconstriction in anesthetized guinea pigs is a useful in vivo model for evaluating the bronchodilating effect of anti-asthmatic drugs.