title: Does the length dependency of airway smooth muscle force contribute to airway hyperresponsiveness?
abstract: Airway wall remodeling and lung hyperinflation are two typical features of asthma that may alter the contractility of airway smooth muscle (ASM) by affecting its operating length. The aims of this study were as follows: 1) to describe in detail the "length dependency of ASM force" in response to different spasmogens; and 2) to predict, based on morphological data and a computational model, the consequence of this length dependency of ASM force on airway responsiveness in asthmatic subjects who have both remodeled airway walls and hyperinflated lungs. Ovine tracheal ASM strips and human bronchial rings were isolated and stimulated to contract in response to increasing concentrations of spasmogens at three different lengths. Ovine tracheal strips were more sensitive and generated greater force at longer lengths in response to acetylcholine (ACh) and K(+). Equipotent concentrations of ACh were approximately a log less for ASM stretched by 30% and approximately a log more for ASM shortened by 30%. Similar results were observed in human bronchi in response to methacholine. Morphometric and computational analyses predicted that the ASM of asthmatic subjects may be elongated by 6.6-10.4% (depending on airway generation) due to remodeling and/or hyperinflation, which could increase ACh-induced force by 1.8-117.8% (depending on ASM length and ACh concentration) and enhance the increased resistance to airflow by 0.4-4,432.8%. In conclusion, elongation of ASM imposed by airway wall remodeling and/or hyperinflation may allow ASM to operate at a longer length and to consequently generate more force and respond to lower concentration of spasmogens. This phenomenon could contribute to airway hyperresponsiveness.
authors: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Department of Medicine, Université Laval, Québec City, Québec, Canada;
authors: Audrey
authors: A
authors: Lee-Gosselin
authors: Chris D
authors: CD
authors: Pascoe
authors: Christian
authors: C
authors: Couture
authors: Peter D
authors: PD
authors: Paré
authors: Ynuk
authors: Y
authors: Bossé
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D056151:Airway Remodeling / Q000187:drug effects / Q000502:physiology; D001249:Asthma / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D006801:Humans; D016210:Methacholine Chloride / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology*; D011188:Potassium / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology
chemical_list: D016210:Methacholine Chloride; D000109:Acetylcholine; D011188:Potassium
keywords: airway remodeling; asthma; computational modeling; hyperinflation