CONTRIBUTION OF A CHOLINERGIC REFLEX MECHANISM TO ALLERGEN-INDUCED BRONCHIAL HYPERREACTIVITY IN PERMANENTLY INSTRUMENTED, UNRESTRAINED GUINEA-PIGS

1 In conscious, permanently instrumented, unrestrained, ovalbumin-sensitized guinea-pigs the development of allergen-induced bronchial hyperreactivity to histamine- and methacholine-inhalation was investigated after the early as well as after the late asthmatic response. 2 The allergen-induced increase in bronchial reactivity to histamine was significantly higher than to methacholine. 3 The muscarinic receptor antagonist, ipratropium bromide (1.0 mM, 3 min inhalation), blocked methacholine-induced bronchoconstriction and caused a significant 1.7 fold inhibition of the histamine-induced bronchoconstriction of control animals. 4 A lower dose of ipratropium bromide (0.1 mM, 3 min inhalation) had no significant effect on histamine-induced bronchoconstriction in control animals, but significantly reduced the allergen-induced increase in bronchial reactivity to histamine between the early and late asthmatic response. At 1.0 mM ipratropium bromide, no further reduction was observed. 5 These results clearly indicate that an exaggerated cholinergic reflex mechanism contributes to allergen-induced bronchial hyperreactivity to histamine