Bronchial hyperresponsiveness induced by chronic treatment with albuterol: Role of sensory nerves.
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 mg.kg(-1).d(-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.


CONCLUSIONS
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.
Sackler Institute of Pulmonary Pharmacology, Division of Pharmacology and Therapeutics, GKT School of Biomedical Sciences, King's College London, London.
Sandra
S
Keir
Clive
C
Page
Domenico
D
Spina
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000420:Albuterol / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000294:innervation*; D016084:Bronchoconstriction / Q000187:drug effects*; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology; D010525:Peripheral Nerves / Q000502:physiology; D013237:Stereoisomerism
D000318:Adrenergic beta-Agonists; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D000420:Albuterol; D002211:Capsaicin