Bronchial hyperresponsiveness induced by chronic treatment with albuterol: Role of sensory nerves

J Allergy Clin Immunol. 2002 Sep;110(3):388-94. doi: 10.1067/mai.2002.126661.


Background: It has recently been suggested that regular treatment with racemic beta(2)-adrenoceptor agonists might result in bronchial hyperresponsiveness (BHR) to a range of spasmogens, and this might be due to adverse effects of the distomer.

Objective: We sought to determine whether BHR induced by means of continuous exposure to racemic and S-albuterol was mediated by sensory nerves.

Methods: Naive or ovalbumin-sensitized guinea pigs were treated for 10 days with RS-, R-, or S-albuterol (1 through subcutaneously implanted minipumps. Lung function was then determined in response to a number of spasmogens and assessed on the basis of an increase in total airway resistance. A separate group of animals were chronically treated with capsaicin (80 mg/kg) before the albuterol treatment.

Results: Treatment with RS- or S-albuterol increased airway responsiveness to bradykinin, leukotriene C(4), and capsaicin in naive guinea pigs (P <.05) and to histamine and ovalbumin in immunized guinea pigs (P <.05). Chronic treatment with capsaicin prevented the development of RS- and S-albuterol-induced BHR in these models. The bronchodilator efficacy of acute intravenously administered RS-albuterol was unaffected in RS-, R-, or S-albuterol-treated guinea pigs compared with in vehicle-treated animals.

Conclusion: We have provided evidence demonstrating that continuous exposure to RS- and S-albuterol increases bronchial responsiveness to a range of stimuli, an effect not attributed to beta-adrenoceptor occupancy or desensitization. Furthermore, capsaicin-sensitive sensory nerves mediate the development of BHR, at least in part.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / administration & dosage
  • Adrenergic beta-Agonists / chemistry
  • Adrenergic beta-Agonists / pharmacology*
  • Albuterol / administration & dosage
  • Albuterol / chemistry
  • Albuterol / pharmacology*
  • Animals
  • Bronchi / drug effects*
  • Bronchi / innervation*
  • Bronchoconstriction / drug effects*
  • Bronchoconstrictor Agents / pharmacology
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / chemistry
  • Bronchodilator Agents / pharmacology*
  • Capsaicin / pharmacology
  • Dose-Response Relationship, Drug
  • Guinea Pigs
  • Male
  • Neurons, Afferent / physiology
  • Peripheral Nerves / physiology
  • Stereoisomerism


  • Adrenergic beta-Agonists
  • Bronchoconstrictor Agents
  • Bronchodilator Agents
  • Albuterol
  • Capsaicin