CHRONIC EXPOSURE TO A BETA(2)-ADRENOCEPTOR AGONIST INCREASES THE AIRWAY RESPONSE TO METHACHOLINE

Scheduled chronic administration of beta2-adrenoceptor agonist broncho dilators in patients with asthma recently has been reported to be asso ciated with a worsening of symptoms and an increase in bronchial respo nsiveness. We wanted to determine whether a 28-day in vivo exposure to albuterol (beta2-adrenoceptor agonist) altered the response of rabbit airways to the cholinergic agonist methacholine. We found, using in v itro tissue bath techniques, that in mainstem bronchi from rabbits giv en a 28-day exposure to albuterol, maximum contraction to methacholine was increased in the albuterol-treated group (control group = 1.10 +/ - 0.11 g vs. treated group = 1.50 +/- 0.13 g, P < 0.05). The potency ( EC75) was also increased in the albuterol-treated group. The potency f or the control group was 5.6 muM (95% confidence limit: 2.3713 muM) an d was 1.7 muM (95% confidence limit: 1.1-2.8 muM, P < 0.05) for the al buterol-treated group. In a subgroup of animals, maximum contraction t o KCl, a receptor-independent contractile stimulus, was not significan tly different between the groups (control group = 0.79 +/- 0.23 g vs. treated group = 0.82 0.20 g). The potency (EC50) for KCl-induced contr actions was also,not significantly, different between the groups: cont rol = 12 mM (95% confidence limit: 3.3-44 mM) vs. treated 19 mM (95% c onfidence limit: 18-20 mM). These data demonstrate that chronic in viv o exposure to a beta2-adrenoceptor agonist can alter the in vitro tiss ue bath response of airway smooth muscle to methacholine. Therefore, c holinergic mechanisms in the airway smooth muscle appear to be altered by chronic beta2-adrenoceptor agonist exposure. This change in the ai rway smooth muscle response to methacholine may play a role in the inc rease of bronchial responsiveness associated with regular beta2-adreno ceptor agonist use.