Length oscillation induces force potentiation in infant guinea pig airway smooth muscle

Abstract

Deep inspiration counteracts bronchospasm in normal subjects but triggers further bronchoconstriction in hyperresponsive airways. Although the exact mechanisms for this contrary response by normal and hyperresponsive airways are unclear, it has been suggested that the phenomenon is related to changes in force-generating ability of airway smooth muscle after mechanical oscillation. It is known that healthy immature airways of both humans and animals exhibit hyperresponsiveness. We hypothesize that the profile of active force generation after mechanical oscillation changes with maturation and that this change contributes to the expression of airway hyperresponsiveness in juveniles. We examined the effect of an acute sinusoidal length oscillation on the force-generating ability of tracheal smooth muscle from 1 wk, 3 wk, and 2- to 3-mo-old guinea pigs. We found that the length oscillation produced 15-20% initial reduction in active force equally in all age groups. This was followed by a force recovery profile that displayed striking maturation-specific features. Unique to tracheal strips from 1-wk-old animals, active force potentiated beyond the maximal force generated before oscillation. We also found that actin polymerization was required in force recovery and that prostanoids contributed to the maturation-specific force potentiation in immature airway smooth muscle. Our results suggest a potentiated mechanosensitive contractile property of hyperresponsive airway smooth muscle. This can account for further bronchoconstriction triggered by deep inspiration in hyperresponsive airways.

Fig. 1

Reduction in isometric force due to length oscillation measured in 1-wk-old (1-wk), 3-wk-old (3-wk), and 2- to 3-mo-old (adult) guinea pigs. Bars indicate the mean values of reduction expressed as %F_max, error bars indicate SE. F_max, maximal active force measured before length oscillation.

Fig. 2

Adaptation of isometric force measured in the 3 age groups. Data points show mean values and SE expressed as %F_max. Data points at 0 min indicate force generated immediately after the termination of length oscillation. Dotted line at 100% denotes the level of F_max measured before oscillation.

Fig. 3

Effect of cytochalasin D (10⁻⁷ M) on force reduction following length oscillation (A) and adaptation of isometric force (B). Data show means and SE expressed as %F_max. Dotted line at 100% denotes the level of F_max.

Fig. 4

Comparison of adaptation process between control and treatment with jasplakinolide (5 ×10⁻⁷ M) measured in tracheal strips from adult guinea pigs. Data points show means and SE expressed as %F_max. Dotted line at 100% denotes the level of F_max.

Fig. 5

Effect of indomethacin (Indo; 10⁻⁵ and 10⁻⁴ M) on force reduction (A) and force adaptation (B) measured in tracheal strips from 1-wk guinea pigs. Data points show means and SE expressed as %F_max. Dotted line at 100% indicates the level of F_max.

Fig. 6

Effect of indomethacin (Indo; 10⁻⁴ M) on force adaptation in tracheal strips from adult guinea pigs. Data show means and SE expressed as %F_max. Dotted line at 100% indicates the level of F_max.