In:
Journal of Applied Physiology, American Physiological Society, Vol. 118, No. 6 ( 2015-03-15), p. 692-698
Abstract:
Airway hyperresponsiveness to a spasmogenic challenge such as methacholine, and an increased baseline tone measured by the reversibility of airway obstruction with a bronchodilator, are two common features of asthma. However, whether the increased tone influences the degree of airway responsiveness to a spasmogen is unclear. Herein, we hypothesized that increased tone augments airway responsiveness in vivo by increasing the contractile capacity of airway smooth muscle (ASM). Anesthetized, tracheotomized, paralyzed, and mechanically ventilated mice were either exposed (experimental group) or not (control group) to tone for 20 min, which was elicited by nebulizing serial small doses of methacholine. Respiratory system resistance was monitored during this period and the peak response to a large cumulative dose of methacholine was then measured at the end of 20 min to assess and compare the level of airway responsiveness between groups. To confirm direct ASM involvement, the contractile capacity of excised murine tracheas was measured with and without preexposure to tone elicited by either methacholine or a thromboxane A 2 mimetic (U46619). Distinct spasmogens were tested because the spasmogens liable for increased tone in asthma are likely to differ. The results indicate that preexposure to tone increases airway responsiveness in vivo by 126 ± 37% and increases the contractile capacity of excised tracheas ex vivo by 23 ± 4% for methacholine and 160 ± 63% for U46619. We conclude that an increased tone, regardless of whether it is elicited by a muscarinic agonist or a thromboxane A 2 mimetic, may contribute to airway hyperresponsiveness by increasing the contractile capacity of ASM.
Type of Medium:
Online Resource
ISSN:
8750-7587
,
1522-1601
DOI:
10.1152/japplphysiol.00645.2014
Language:
English
Publisher:
American Physiological Society
Publication Date:
2015
detail.hit.zdb_id:
1404365-8
SSG:
12
SSG:
31
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