Dissociation between bronchial hyperreactivity in vivo and reduced beta-adrenoceptor sensitivity in vitro in allergen-challenged guinea pigs.

Abstract

In a recently developed guinea pig model of allergic asthma, we investigated the relationships between allergen-induced bronchial hyperreactivity in vivo, tracheal smooth muscle function in vitro, and the number of inflammatory cells in the bronchoalveolar lavage. At 6 h after allergen provocation (after the early asthmatic reaction) bronchial hyperreactivity to histamine aerosol was observed, which was still present, but reduced, at 24 h after the challenge (after the late asthmatic reaction). The severity of bronchial hyperreactivity at 6 h and at 24 h after each of four daily allergen provocations was progressively reduced. The contractile properties of tracheal smooth muscle preparations in response to methacholine or histamine were not changed at 6 h and 24 h after a single allergen provocation, as well as at 24 h after the fourth of the repeated provocations. However, the sensitivity to isoprenaline-induced relaxation of a half-maximal contraction obtained with methacholine or histamine was significantly reduced at 24 h after either a single or the fourth of the repeated provocations. The time course of the reduced beta-adrenoceptor sensitivity in vitro did not correlate with that of bronchial hyperreactivity in vivo. However, it was parallelled by a progressive infiltration of inflammatory cells in the airways, suggesting that mediators from these cells may decrease airway smooth muscle beta-adrenoceptor sensitivity.