The role of airway smooth muscle during an attack of asthma simulated in vitro.
Excessive narrowing of airways in response to contractile agonists is a characteristic feature of asthma. We hypothesized that airway smooth muscle (ASM) adaptation to short lengths could contribute to exaggerated airway narrowing during an acute attack of asthma by allowing the muscle to regain its ability to generate maximal force at a shortened length. To test this hypothesis we mimicked, in vitro, the sequence of contractile events that would occur during a spontaneous attack of asthma. Trachealis muscle was challenged with carbachol (300 nM, submaximal dose) and allowed to shorten to approximately half of its original length. After 30 min of adaptation at the shortened length in the presence of carbachol, muscle force, amount and rate of shortening in response to electrical stimulation were compared with corresponding values obtained from control experiments during which the ASM was not adapted to the short length. After adaptation at the shortened length the developed force, amount and rate of shortening increased by 1.93 +/- 0.08-, 1.57 +/- 0.12-, and 1.75 +/- 0.2-fold, respectively. Shortening of ASM in response to contractile agonists can lead to adaptation of the muscle to the shortened length that, in turn, can result in further shortening and the potential for airway closure.
McParland
Brent E
BE
Department of Medicine, James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research, St. Paul's Hospital/Providence Health Care, University of British Columbia, Vancouver, British Columbia, Canada.
Tait
Ross R
RR
Paré
Peter D
PD
Seow
Chun Y
CY
D000222:Adaptation, Physiological; D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects / Q000503:physiopathology*; D002217:Carbachol / Q000494:pharmacology; D003251:Constriction, Pathologic / Q000503:physiopathology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007551:Isotonic Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology*; D013552:Swine; D014132:Trachea / Q000187:drug effects / Q000503:physiopathology*
D002217:Carbachol