Collagenase increases shortening of human bronchial smooth muscle in vitro

Am J Respir Crit Care Med. 1995 Nov;152(5 Pt 1):1513-7. doi: 10.1164/ajrccm.152.5.7582286.

Abstract

The recent demonstration of increased shortening of asthmatic airway smooth muscle could result from increased contractility of the muscle itself or from a decreased load that must be overcome by the smooth muscle to shorten. To evaluate the role of smooth muscle-associated extracellular matrix in limiting smooth muscle responses, we investigated the effect of collagenase on the mechanical responses of human bronchial smooth muscle strips. Contractile responses of second- to fourth-generation bronchi were evoked by electrical field stimulation, and measurements of length and tension were made at preloads between 0 and 2.5 g. The passive tension, active isometric, and isotonic responses were obtained at each preload before and after 90 min of incubation with 20 U/ml collagenase. Shortening to 10(-4) M histamine was also measured. Collagenase treatment caused a significant decrease in passive tension, with the most pronounced change occurring below Lmax (optimal length for force generation). At optimal lengths for shortening, the degree of shortening, expressed as a percentage of starting length, increased significantly from 8.9 +/- 1.4% before to 13.8 +/- 2.9% after collagenase treatment (n = 7) (p < 0.02). Shortening to histamine also increased from 14.3 +/- 2.5% before to 23.5 +/- 5.3% after collagenase treatment (n = 7) (p < 0.02). These results suggest that degradation of the collagenous matrix surrounding muscle in the airway wall reduces the load on the muscle, allowing increased smooth muscle shortening.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Aged
  • Biomechanical Phenomena
  • Bronchi / drug effects
  • Bronchi / physiology
  • Clostridium / enzymology
  • Female
  • Histamine / analogs & derivatives
  • Histamine / pharmacology
  • Humans
  • In Vitro Techniques
  • Male
  • Microbial Collagenase / pharmacology*
  • Middle Aged
  • Muscle Contraction / drug effects*
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / physiology
  • Myography / instrumentation
  • Myography / methods
  • Papaverine / pharmacology

Substances

  • Histamine
  • Papaverine
  • Microbial Collagenase
  • Acetylcholine
  • histamine phosphate