Force oscillations simulating breathing maneuvers do not prevent force adaptation.

Airway inflammation in patients with asthma exposes the airway smooth muscle (ASM) to a variety of spasmogens. These spasmogens increase ASM tone, which can lead to force adaptation. Length oscillations of ASM, which occur in vivo due to breathing maneuvers, can attenuate force adaptation. However, in the presence of tone, the force oscillations required to achieve these length oscillations may be unphysiologic (i.e., magnitude greater than the ones achieved due to the swings in transpulmonary pressure required for breathing). In the present study, we applied force oscillations simulating the tension oscillations experienced by the wall of a fourth-generation airway during tidal breathing with or without deep inspirations (DI) to ASM. The goal was to investigate whether force adaptation occurs in conditions mimicking breathing maneuvers. Tone was induced by carbachol (average, 20 nM), and the force-generating capacity of the ASM was assessed at 5-minute intervals before and after carbachol administration using electrical field stimulations (EFS). The results show that force oscillations applied before the introduction of tone had a small effect on the force produced by EFS (declined to 96.8% [P > 0.05] and 92.3% [P < 0.05] with and without DI, respectively). The tone induced by carbachol transiently decreased after a DI and declined significantly (P < 0.05) due to tidal breathing oscillations (25%). These force oscillations did not prevent force adaptation (gain of force of 11.2 ± 2.2 versus 13.5 ± 2.7 and 11.2 ± 3.0% in static versus dynamic conditions with or without DI, respectively). The lack of effect of simulated breathing maneuvers on force adaptation suggests that this gain in ASM force may occur in vivo and could contribute to the development of airway hyperresponsiveness.