You are here:
Vagotomy Reverses Established Allergen-Induced Airway Hyperreactivity to Methacholine in the Mouse
Citation:
McAlexander, M., S. Gavett, M. Kollarik, AND B. Undem. Vagotomy Reverses Established Allergen-Induced Airway Hyperreactivity to Methacholine in the Mouse. Respiratory Physiology and Neurobiology. Elsevier BV, AMSTERDAM, Netherlands, 212:20-24, (2015).
Impact/Purpose:
This study addresses the hypothesis that the airway hyperreactivity associated with acute allergen and particulate matter-induced inflammation in mice is due, at least in part, to an exaggeration in the vagal nerve reflex component of the response to cholinergic stimulation. The study was done to address the neurological mechanisms by which particulate matter and allergens exacerbate respiratory responses in animals. This study showed that the increase in cholinergic responsiveness observed in particulate matter and allergen-exposed mice is due in large part to an increase in the vagal reflex component. This study helps to identify the mechanisms by which particulate matter and allergens affect pulmonary responses, thus contributing to the Agency’s goals of understanding the scientific basis for the health effects of particulate matter, especially in susceptible allergic individuals.
Description:
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.
