Racemic salbutamol administration to guinea-pigs selectively augments airway smooth muscle responsiveness to cholinoceptor agonists.
1. An aim of this study was to investigate whether continuous in vivo administration of a low dose of salbutamol to guinea-pigs alters the responsiveness of airway smooth muscle in vitro. 2. Osmotic minipumps containing a solution of racemic salbutamol were implanted subcutaneously in guinea-pigs. The drug was infused at a dose of 0.2 mg kg(-1) day(-1) for 10 days and, at the end of that time, the trachea was isolated and concentration-response relationships to several contractile agonists were examined. 3. This treatment resulted in significant increases in the maximum tension developed by tracheal preparations in response to cholinoceptor agonists, carbachol and methacholine. 4. Cumulative concentration-response curves for histamine, leukotriene D4, and KCl were similar in tracheal segments from saline-control and salbutamol-infused animals. 5. Time course experiments showed that augmented airway contractile responsiveness to cholinoceptor agonists was reversible within 3 days after cessation of the 10 day salbutamol infusion. 6. Our findings support the hypothesis that beta2-adrenoceptor agonist drugs, administered over time in vivo, induce a transient hyperresponsiveness of airway smooth muscle to cholinergic bronchoconstrictor stimuli.
Loss
J R
JR
Department of Pharmaceutical Sciences, University of the Sciences in Philadelphia, 600 South Forty-third Street, Philadelphia, PA 19104-4495, USA.
Hock
R S
RS
Farmer
S G
SG
Orzechowski
R F
RF
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D018679:Cholinergic Agonists / Q000494:pharmacology*; D004357:Drug Synergism; D006168:Guinea Pigs; D007279:Injections, Subcutaneous; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects*; D012137:Respiratory System / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D018679:Cholinergic Agonists; D018721:Muscarinic Agonists; D000420:Albuterol