Adaptation of airway smooth muscle to basal tone: relevance to airway hyperresponsiveness.
Lung inflammation and airway hyperresponsiveness (AHR) are hallmarks of asthma, but their interrelationship is unclear. Excessive shortening of airway smooth muscle (ASM) in response to bronchoconstrictors is likely an important determinant of AHR. Hypercontractility of ASM could stem from a change in the intrinsic properties of the muscle, or it could be due to extrinsic factors such as chronic exposure of the muscle to inflammatory mediators in the airways. The latter could be the link between lung inflammation and AHR. The present study was designed to examine the influence of chronic exposure to a contractile agonist on the force-generating capacity of ASM. Force generation in response to electric field stimulation (EFS) was measured in ovine trachealis with or without a basal tone induced by acetylcholine (ACh). While the tone was maintained, the EFS-induced force decreased transiently but increased over time to reach a plateau in approximately 50 minutes. The total force (ACh tone + EFS force) increased monotonically and in proportion to ACh concentration. The results indicate that the muscle adapted to the basal tone and regained its contractile ability in response to a second stimulus (EFS) over time. Analysis suggests that this is due to a cytoskeletal transformation that allows the cytoskeleton to bear force, thus freeing up actomyosin crossbridges to generate more force. Force adaptation in ASM as a consequence of prolonged exposure to the many spasmogens found in asthmatic airways could be a mechanism contributing to AHR seen in asthma.
Bossé
Ynuk
Y
the James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research/St. Paul's Hospital, Room 166-1081, Burrard Street, Vancouver, BC, V6Z 1Y6 Canada. ybosse@mrl.ubc.ca
Chin
Leslie Y M
LY
Paré
Peter D
PD
Seow
Chun Y
CY
D000109:Acetylcholine / Q000494:pharmacology; D000403:Airway Resistance / Q000502:physiology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D012137:Respiratory System; D012756:Sheep; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D000109:Acetylcholine