title: Collagenase increases shortening of human bronchial smooth muscle in vitro.
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.
authors.affiliation: UBC Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, British Columbia, Canada.
authors.forename: A M
authors.initials: AM
authors.lastname: Bramley
authors.forename: C R
authors.initials: CR
authors.lastname: Roberts
authors.forename: R R
authors.initials: RR
authors.lastname: Schellenberg
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D001696:Biomechanical Phenomena; D001980:Bronchi / Q000187:drug effects / Q000502:physiology; D003013:Clostridium / Q000201:enzymology; D005260:Female; D006632:Histamine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D003012:Microbial Collagenase / Q000494:pharmacology*; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009213:Myography / Q000295:instrumentation / Q000379:methods; D010208:Papaverine / Q000494:pharmacology
chemical_list: D006632:Histamine; D010208:Papaverine; D003012:Microbial Collagenase; D000109:Acetylcholine; C027556:histamine phosphate