title: Vagotomy reverses established allergen-induced airway hyperreactivity to methacholine in the mouse.
abstract: We evaluated the role of vagal reflexes in a mouse model of allergen-induced airway hyperreactivity. Mice were actively sensitized to ovalbumin then exposed to the allergen via inhalation. Prior to ovalbumin inhalation, mice also received intratracheally-instilled particulate matter in order to boost the allergic response. In control mice, methacholine (i.v.) caused a dose-dependent increase in respiratory tract resistance (RT) that only modestly decreased if the vagi were severed bilaterally just prior to the methacholine challenge. Sensitized and challenged mice, however, manifested an airway reactivity increase that was abolished by severing the vagi prior to methacholine challenge. In an innervated ex vivo mouse lung model, methacholine selectively evoked action potential discharge in a subset of distension-sensitive A-fibers. These data support the hypothesis that the major component of the increased airway reactivity in inflamed mice is due to a vagal reflex initiated by activation of afferent fibers, even in response to a direct (i.e., smooth muscle)-acting muscarinic agonist.
authors.affiliation: Integrated Toxicology Program, Duke University, Durham, NC, United States.
authors.forename: M Allen
authors.initials: MA
authors.lastname: McAlexander
authors.affiliation: EPHD, NHEERL, United States Environmental Protection Agency, Research Triangle Park, NC, United States.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Gavett
authors.affiliation: Johns Hopkins School of Medicine, Baltimore, MD, United States.
authors.forename: Marian
authors.initials: M
authors.lastname: Kollarik
authors.affiliation: Johns Hopkins School of Medicine, Baltimore, MD, United States. Electronic address: Bundem@jhmi.edu.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Undem
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000485:Allergens / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D018893:Bronchoalveolar Lavage / Q000379:methods; D016085:Bronchoconstrictor Agents / Q000627:therapeutic use; D005260:Female; D007249:Inflammation / Q000139:chemically induced; D016210:Methacholine Chloride / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000188:drug therapy / Q000601:surgery*; D014628:Vagotomy / Q000379:methods*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
chemical_list: D000485:Allergens; D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride
keywords: Airway hyperreactivity; Allergic inflammation; Particulate matter; Reflex; Vagotomy; Vagus nerve
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