PHARMACOLOGICAL MODULATION OF THE MECHANICAL RESPONSE OF AIRWAY SMOOTH-MUSCLE TO LENGTH OSCILLATION

Stretch and retraction of the airways caused by changes in lung volume may play an important role in regulating airway reactivity. We studie d the effects of different pharmacological stimuli on airway smooth mu scle to determine whether the muscle behavior during length oscillatio n can be modulated pharmacologically and to evaluate the role of diffe rent activation mechanisms in determining its behavior during the osci llation. Active force decreased below the static isometric force durin g the shortening phase of length oscillation, resulting in an overall depression of force during the length oscillation cycle. This pattern of response was unaffected by the contractile stimulus or level of act ivation, suggesting that it was caused by a mechanism that is independ ent of the level of activation of cross bridges. The normalized area o f the length-force hysteresis loop (hysteresivity) differed depending on the stimulus used for contraction. Effects of different stimuli on hysteresivity were not correlated with their effects on isotonic short ening velocity or isometric force, suggesting that the pharmacological modulation of the behavior of airway smooth muscle during length osci llation at these amplitudes cannot be accounted for by the effects on the cross-bridge cycling rate.