Racemic salbutamol administration to guinea‐pigs selectively augments airway smooth muscle responsiveness to cholinoceptor agonists

Abstract

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.

Dichrostachys cinerea (L.) Wight et Arn (Mimosaceae) hydro-alcoholic extract action on the contractility of tracheal smooth muscle isolated from guinea-pig

“…Similar results were obtained with the pharmacological reference drug, salbutamol, a short-acting β 2 -adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary [30]. The table 2 shows the effect of cumulative doses of salbutamol on the GPTPs.…”

“…The loss of M 2 muscarinic receptor function in children and adults happens during antigen bronchoprovocation or during exposition of asthmatics to ozone. The research findings support the hypothesis that beta2-adrenoceptor agonist drugs, administered over time in vivo or in vitro , induce a transient hyperresponsiveness of airway smooth muscle to cholinergic bronchoconstrictor stimuli [29,30]. Histamine-evoked broncho-constriction is due to the activation of H 1 -histaminergic receptors and is blocked by antihistaminergic drugs such as promethazine [31,32].…”

Rosiglitazone reverses salbutamol‐induced β2‐adrenoceptor tolerance in airway smooth muscle

“…As selective airway smooth muscle hyperresponsiveness to cholinergic stimulation has been reported after chronic exposure to salbutamol (Loss et al ., 2001), tracheal contractility to 0.3 µmol·L −1 carbachol was measured in the different treatment groups.…”