TY - JOUR
T1 - Vagotomy reverses established allergen-induced airway hyperreactivity to methacholine in the mouse
AU - McAlexander, M. Allen
AU - Gavett, Stephen H.
AU - Kollarik, Marian
AU - Undem, Bradley J.
N1 - Funding Information:
The authors wish to thank Najwa Haykal-Coates for expert technical assistance. Funding provided by US EPA-Duke University Cooperative agreement # CT826514 and National Institute of Health grant HL038095 .
Publisher Copyright:
© 2015 Published by Elsevier B.V.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - 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.
AB - 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.
KW - Airway hyperreactivity
KW - Allergic inflammation
KW - Particulate matter
KW - Reflex
KW - Vagotomy
KW - Vagus nerve
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U2 - 10.1016/j.resp.2015.03.007
DO - 10.1016/j.resp.2015.03.007
M3 - Article
C2 - 25842220
AN - SCOPUS:84928332391
SN - 1569-9048
VL - 212-214
SP - 20
EP - 24
JO - Respiratory Physiology and Neurobiology
JF - Respiratory Physiology and Neurobiology
ER -