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. actin polymerization; deep inspiration; hyperresponsive airways; ontogenesis; prostanoids AIRWAY HYPERRESPONSIVENESS is characterized by increased sensitivity of the tracheobronchial tree to contractile stimuli as well as an increased capacity for airway narrowing. Altered contractility of airway smooth muscle (ASM) is one of the mechanisms potentially responsible for increased airway sensitivity and maximal response. The involvement of ASM in the pathogenesis of airway hyperresponsiveness has long been controversial. However, both the capacity and velocity of shortening have been shown to be elevated in ASM from hyperresponsive airways (14,17). Increased ASM contractility shown in young animals suggests a central role for ASM also in juvenile airway hyperresponsiveness (8). It becomes, therefore, particularly important to study the mechanisms by which ASM function changes with maturation and whether this has a role in juvenile hyperresponsiveness and childhood asthma.An important feature of altered airway function in asthma is the inability of deep inspiration (DI) to improve airway function (37). DI could even induce bronchoconstriction in asthmatic subjects (2, 19). It has been convincingly shown that DI reverses bronchoconstriction in normal subjects by stretching contracted ASM (22). The protective effect of DI gained considerable research interest in recent years due to reports that showed a DI before the administration of a cont...

Expression of smooth muscle and extracellular matrix proteins in relation to airway function in asthma

“…A higher level of a-SM-actin expression may indicate more actin monomers that can form longer actin filaments by polymerization in the asthmatic inflammatory environment. 33 Smooth muscle cells with longer actin filaments show a more elastic behavior, which can generate force even after being stretched, 34,35 and may therefore increase airway hyperresponsiveness. Desmin, on the other hand, is an intermediate filament, present in dense bodies, and stabilizes the contractile units and participates in stress transmission between contractile units and anchorage sites linking to the extracellular matrix.…”

Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma

“…ASM becomes progressively less compliant but more sensitive to acetylcholine with maturation in sheep [212], while the shortening velocity and passive stiffness of guinea pig trachealis both increase in the first 3 weeks of life and then decline [213,214]. More significantly, the force-generating ability of ASM is potentiated by stretch in infant guinea pigs but not in adult animals [215], and appears to be related to maturational changes in the release of prostanoids [216]. These findings may have relevance to the observations of WEIST et al [206], who showed that airway reactivity in healthy infants is not only greater than that in healthy adults, but is also insensitive to deep inspiration, similar to the situation in asthmatic adults [18] and in passively sensitised human bronchi [217].…”

Histopathology and growth kinetics of influenza viruses (H1N1 and H3N2) in the upper and lower airways of guinea pigs

“…In this respect, the guinea pig is unique because its airway innervation is very similar to that of humans (Wang et al, 2005). Moreover, guinea pigs are widely used in pulmonary pharmacology because their responses to various mediators and drugs are more similar to that of the human airway (Ressmeyer et al, 2006).…”