DISSOCIATION BETWEEN BRONCHIAL HYPERREACTIVITY IN-VIVO AND REDUCED BETA-ADRENOCEPTOR SENSITIVITY IN-VITRO IN ALLERGEN-CHALLENGED GUINEA-PIGS

In a recently developed guinea pig model of allergic asthma, we invest igated the relationships between allergen-induced bronchial hyperreact ivity in vivo, tracheal smooth muscle function in vitro, and the numbe r of inflammatory cells in the bronchoalveolar lavage. At 6 h after al lergen provocation (after the early asthmatic reaction) bronchial hype rreactivity to histamine aerosol was observed, which was still present , but reduced, at 24 h after the challenge (after the late asthmatic r eaction). The severity of bronchial hyperreactivity at 6 h and at 24 h after each of four daily allergen provocations was progressively redu ced. 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 isop renaline-induced relaxation of a half-maximal contraction obtained wit h methacholine or histamine was significantly reduced at 24 h after ei ther a single or the fourth of the repeated provocations. The time cou rse of the reduced beta-adrenoceptor sensitivity in vitro did not corr elate 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 airw ay smooth muscle beta-adrenoceptor sensitivity.