A 'Good' muscle in a 'Bad' environment: The importance of airway smooth muscle force adaptation to airway hyperresponsiveness

Bossé, Y; Chapman, DG; Paré, PD; King, GG; Salome, CM

A 'Good' muscle in a 'Bad' environment: The importance of airway smooth muscle force adaptation to airway hyperresponsiveness

Bossé, Y Chapman, DG

Paré, PD King, GG Salome, CM

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Publication Type:: Journal Article
Citation:: Respiratory Physiology and Neurobiology, 2011, 179 (2-3), pp. 269 - 275
Issue Date:: 2011-01-01

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Field	Value	Language
dc.contributor.author	Bossé, Y	en_US
dc.contributor.author	Chapman, DG https://orcid.org/0000-0002-8211-1817	en_US
dc.contributor.author	Paré, PD	en_US
dc.contributor.author	King, GG	en_US
dc.contributor.author	Salome, CM	en_US
dc.date.available	2011-09-06	en_US
dc.date.issued	2011-01-01	en_US
dc.identifier.citation	Respiratory Physiology and Neurobiology, 2011, 179 (2-3), pp. 269 - 275	en_US
dc.identifier.issn	1569-9048	en_US
dc.identifier.uri	http://hdl.handle.net/10453/116723
dc.description.abstract	Asthma is characterized by airway inflammation, with a consequent increase in spasmogens, and exaggerated airway narrowing in response to stimuli, termed airway hyperresponsiveness (AHR). The nature of any relationship between inflammation and AHR is less clear. Recent ex vivo data has suggested a novel mechanism by which inflammation may lead to AHR, in which increased basal ASM-tone, due to the presence of spasmogens in the airways, may "strengthen" the ASM and ultimately lead to exaggerated airway narrowing. This phenomenon was termed "force adaptation" [Bossé, Y., Chin, L.Y., Paré, P.D., Seow, C.Y., 2009. Adaptation of airway smooth muscle to basal tone: relevance to airway hyperresponsiveness. Am. J. Respir. Cell Mol. Biol. 40, 13-18]. However, it is unknown whether the magnitude of the effect of force adaptation ex vivo could contribute to exaggerated airway narrowing in vivo. Our aim was to utilize a computational model of ASM shortening in order to quantify the potential effect of force adaptation on airway narrowing when all other mechanical factors were kept constant. The shortening in the model is dictated by a balance between physiological loads and ASM force-generating capacity at different lengths. The results suggest that the magnitude of the effect of force adaptation on ASM shortening would lead to substantially more airway narrowing during bronchial challenge at any given airway generation. We speculate that the increased basal ASM-tone in asthma, due to the presence of inflammation-derived spasmogens, produces an increase in the force-generating capacity of ASM, predisposing to AHR during subsequent challenge. © 2011 Elsevier B.V.	en_US
dc.relation.ispartof	Respiratory Physiology and Neurobiology	en_US
dc.relation.isbasedon	10.1016/j.resp.2011.09.003	en_US
dc.subject.classification	Physiology	en_US
dc.subject.mesh	Muscle, Smooth	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Bronchial Hyperreactivity	en_US
dc.subject.mesh	Adaptation, Physiological	en_US
dc.subject.mesh	Muscle Tonus	en_US
dc.subject.mesh	Models, Theoretical	en_US
dc.title	A 'Good' muscle in a 'Bad' environment: The importance of airway smooth muscle force adaptation to airway hyperresponsiveness	en_US
dc.type	Journal Article
utslib.citation.volume	2-3	en_US
utslib.citation.volume	179	en_US
utslib.for	1109 Neurosciences	en_US
utslib.for	1116 Medical Physiology	en_US
utslib.for	1102 Cardiorespiratory Medicine and Haematology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	2-3	en_US
pubs.publication-status	Published	en_US
pubs.volume	179	en_US

Abstract:

Asthma is characterized by airway inflammation, with a consequent increase in spasmogens, and exaggerated airway narrowing in response to stimuli, termed airway hyperresponsiveness (AHR). The nature of any relationship between inflammation and AHR is less clear. Recent ex vivo data has suggested a novel mechanism by which inflammation may lead to AHR, in which increased basal ASM-tone, due to the presence of spasmogens in the airways, may "strengthen" the ASM and ultimately lead to exaggerated airway narrowing. This phenomenon was termed "force adaptation" [Bossé, Y., Chin, L.Y., Paré, P.D., Seow, C.Y., 2009. Adaptation of airway smooth muscle to basal tone: relevance to airway hyperresponsiveness. Am. J. Respir. Cell Mol. Biol. 40, 13-18]. However, it is unknown whether the magnitude of the effect of force adaptation ex vivo could contribute to exaggerated airway narrowing in vivo. Our aim was to utilize a computational model of ASM shortening in order to quantify the potential effect of force adaptation on airway narrowing when all other mechanical factors were kept constant. The shortening in the model is dictated by a balance between physiological loads and ASM force-generating capacity at different lengths. The results suggest that the magnitude of the effect of force adaptation on ASM shortening would lead to substantially more airway narrowing during bronchial challenge at any given airway generation. We speculate that the increased basal ASM-tone in asthma, due to the presence of inflammation-derived spasmogens, produces an increase in the force-generating capacity of ASM, predisposing to AHR during subsequent challenge. © 2011 Elsevier B.V.

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http://hdl.handle.net/10453/116723