Chronic exposure to a beta 2-adrenoceptor agonist increases the airway response to methacholine.
Scheduled chronic administration of beta 2-adrenoceptor agonist bronchodilators in patients with asthma recently has been reported to be associated with a worsening of symptoms and an increase in bronchial responsiveness. We wanted to determine whether a 28-day in vivo exposure to albuterol (beta 2-adrenoceptor agonist) altered the response of rabbit airways to the cholinergic agonist methacholine. We found, using in vitro tissue bath techniques, that in mainstem bronchi from rabbits given 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 for the control group was 5.6 microM (95% confidence limit: 2.3-13 microM) and was 1.7 microM (95% confidence limit: 1.1-2.8 microM, P < 0.05) for the albuterol-treated group. In a subgroup of animals, maximum contraction to KCl, a receptor-independent contractile stimulus, was not significantly 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 contractions was also not significantly different between the groups: control = 12 mM (95% confidence limit: 3.3-44 mM) vs. treated 19 mM (95% confidence limit: 18-20 mM). These data demonstrate that chronic in vivo exposure to a beta 2-adrenoceptor agonist can alter the in vitro tissue bath response of airway smooth muscle to methacholine.(ABSTRACT TRUNCATED AT 250 WORDS)
Witt-Enderby
P A
PA
Department of Pharmacology, College of Medicine, University of Arizona Health Sciences Center, Tucson 85724.
Yamamura
H I
HI
Halonen
M
M
Palmer
J D
JD
Bloom
J W
JW
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000187:drug effects; D005260:Female; D005280:Fenoterol / Q000494:pharmacology; D008297:Male; D008688:Methacholine Compounds / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D011950:Receptors, Cholinergic / Q000187:drug effects; D012143:Respiratory Physiological Phenomena
D000318:Adrenergic beta-Agonists; D008688:Methacholine Compounds; D011950:Receptors, Cholinergic; D005280:Fenoterol; D011189:Potassium Chloride; D000420:Albuterol