Peripheral Airway Smooth Muscle, but Not the Trachealis, Is Hypercontractile in an Equine Model of Asthma

Am J Respir Cell Mol Biol. 2016 May;54(5):718-27. doi: 10.1165/rcmb.2015-0180OC.

Abstract

Heaves is a naturally occurring equine disease that shares many similarities with human asthma, including reversible antigen-induced bronchoconstriction, airway inflammation, and remodeling. The purpose of this study was to determine whether the trachealis muscle is mechanically representative of the peripheral airway smooth muscle (ASM) in an equine model of asthma. Tracheal and peripheral ASM of heaves-affected horses under exacerbation, or under clinical remission of the disease, and control horses were dissected and freed of epithelium to measure unloaded shortening velocity (Vmax), stress (force/cross-sectional area), methacholine effective concentration at which 50% of the maximum response is obtained, and stiffness. Myofibrillar Mg(2+)-ATPase activity, actomyosin in vitro motility, and contractile protein expression were also measured. Horses with heaves had significantly greater Vmax and Mg(2+)-ATPase activity in peripheral airway but not in tracheal smooth muscle. In addition, a significant correlation was found between Vmax and the time elapsed since the end of the corticosteroid treatment for the peripheral airways in horses with heaves. Maximal stress and stiffness were greater in the peripheral airways of the horses under remission compared with controls and the horses under exacerbation, potentially due to remodeling. Actomyosin in vitro motility was not different between controls and horses with heaves. These data demonstrate that peripheral ASM is mechanically and biochemically altered in heaves, whereas the trachealis behaves as in control horses. It is therefore conceivable that the trachealis muscle may not be representative of the peripheral ASM in human asthma either, but this will require further investigation.

Keywords: airway hyperresponsiveness; airway smooth muscle; asthma; smooth muscle mechanics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Animals
  • Asthma / physiopathology*
  • Blotting, Western
  • Ca(2+) Mg(2+)-ATPase / metabolism
  • Contractile Proteins / metabolism
  • Disease Models, Animal
  • Female
  • Horse Diseases / physiopathology*
  • Horses
  • Male
  • Methacholine Chloride
  • Muscle Contraction / physiology*
  • Muscle, Smooth / physiopathology*
  • Myofibrils / metabolism
  • Myosin Heavy Chains / metabolism
  • Myosins / metabolism
  • Respiratory Mechanics / physiology
  • Trachea / physiopathology*

Substances

  • Contractile Proteins
  • Methacholine Chloride
  • Ca(2+) Mg(2+)-ATPase
  • Myosin Heavy Chains
  • Myosins