Relaxation of guinea pig trachealis during electrical  field stimulation increases with age

Chitano, Pasquale; Cox, Carrie M.; Murphy, Thomas M.

doi:10.1152/japplphysiol.00688.2001

Cited by 25 publications

(38 citation statements)

References 25 publications

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“…It is known that prostanoids exert on ASM both relaxing and contractile actions with PGE 2 and PGI 2 mainly acting as relaxing factors (23). Chitano et al (6) showed that whereas ASM from adult guinea pigs relaxes to the baseline level while the stimulation is ongoing, 1-wk ASM maintains the contractile state throughout the stimulation. In the presence of indomethacin, 1-wk ASM is able to spontaneous relax like adult muscle strips.…”

Section: Discussionmentioning

confidence: 99%

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

Wang¹,

Chitano²,

Murphy³

2005

American Journal of Physiology-Lung Cellular and Molecular Phys

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-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...

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Section: Discussionmentioning

confidence: 99%

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

Wang¹,

Chitano²,

Murphy³

2005

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…In guinea-pigs, CHITANO and co-workers [10,21] have shown that isometric relaxation of electrically stimulated TSM is decreased in 1-week-old animals compared with 3-week and 3-month-old animals while calculated maximum shortening velocity extrapolated at zero-load is reduced in adults. These results suggest that increased velocity of shortening and decreased isometric relaxing capacity could contribute, at least in part, to the greater incidence of AHR reported in children and juvenile animals [8].…”

Section: Relaxation In Ahrmentioning

confidence: 99%

“…Thus, from a mechanical point of view, the electrically stimulated TSM of rats behaves like canine [24,25], porcine [26], mouse [27] or rabbit [28] TSM and differs from bronchial smooth muscle of humans [14] and TSM of guinea-pigs [10,29], which are both known to exhibit active resting tension. The present data clearly indicate that innate differences in airway responsiveness could not be attributed to differences in active resting tension level in the rat strains under study.…”

Section: Isotonic Relaxation In Fisher and Lewis Ratsmentioning

confidence: 99%

“…Spontaneous relaxation must be differentiated from pharmacological relaxation. The former occurs because of the attenuation or cessation of a contractile stimulus and consists of mechanical events driven by forces that bring the tissue to its original mechanical equilibrium [10]. The latter is induced by pharmacological agents (called bronchodilators) that act either directly on ASM or by inhibiting neural pathways [11].…”

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confidence: 99%

“…While pharmacological relaxation has been extensively studied, almost exclusively in isometric preparations, spontaneous relaxation has been rarely investigated. In sensitised dogs, it has been shown that spontaneous isotonic relaxation of electrically stimulated bronchial smooth muscle was prolonged [12,13], suggesting that factors operating during electrical stimulation might affect ASM relaxation and contribute to the AHR of sensitised tissue [10]. In spontaneous, inherited, genetically determined AHR, spontaneous relaxation remains to be investigated.…”

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confidence: 99%

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Relaxation of tracheal smooth muscle is impaired in innate airway hyperresponsiveness

Blanc

Coirault²,

Oliviéro³

et al. 2009

Eur Respir J

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The current study was designed to determine whether the nonspecific in vivo airway hyperresponsiveness of the inbred Fisher F-344 rat strain is associated with impaired spontaneous relaxation of airway smooth muscle.Strips of the posterior portion of the trachea from 10 adult Fisher and 10 adult Lewis rats were electrically stimulated at pH 7.4, 2.5 mM Ca 2+ concentration, at 37uC. Both isotonic and isometric relaxations of tracheal smooth muscle (TSM) were investigated. Half time for isotonic relaxation at preload was markedly prolonged in Fisher rats (8.33¡3.21 s) compared with Lewis rats (3.53¡0.54 s; p,0.001). Maximum lengthening velocity at preload and peak rate of isometric tension decline were significantly decreased in Fisher rats compared with Lewis rats. The ratio of shortening velocity to lengthening velocity at preload, as well as the ratio of the isometric peak rates of tension development to tension decline were higher in Fisher rat TSM than in Lewis rat TSM. These differences were associated with a six-fold higher expression of myosin light chain kinase in Fisher rats than in Lewis rats.In Fisher rats, these results suggest that innate airway hyperresponsiveness is associated with both a reduced level and a slower rate of TSM spontaneous relaxation, promoting maintenance of airway constriction.

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Mechanisms determining cholinergic neural responses in airways of young and mature rabbits

Larsen

Loader

Nguyen

et al. 2004

Pediatric Pulmonology

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Neural pathways help control airway caliber and responsiveness. Yet little is known of how neural control changes as a function of development. In rabbits, we found electrical field stimulation (EFS) of airway nerves led to more marked contractile responses in 2- vs. 13-week-old animals. This enhanced response to EFS may be due to prejunctional, junctional, and/or postjunctional neural mechanisms. We assessed these mechanisms in airways of 2- and 13-week-old rabbits. The contractile responses to methacholine did not differ in the groups, suggesting postjunctional neural events are not primarily responsible for differing responses to EFS. To address junctional events, acetylcholinesterase (AChE) was measured (spectrophotometry). AChE was elevated in 2-week-olds. However, this should lead to less and not greater responses. Prejunctionally, EFS-induced acetylcholine (ACh) release was assessed by HPLC. Airways of 2-week-old rabbits released significantly more ACh than airways from mature rabbits. Choline acetyltransferase, a marker of cholinergic nerves, was not different between groups, suggesting that more ACh release in young rabbits was not due to increased nerve density. ACh release in the presence of polyarginine increased significantly in both groups, supporting the presence of functional muscarinic autoreceptors (M2) at both ages. Because substance P (SP) increases release of ACh, SP was measured by ELISA. This neuropeptide was significantly elevated in airways of younger rabbits. Nerve growth factor (NGF) increased SP and was also significantly increased in airways from younger rabbits. This work suggests that increases in EFS-induced responsiveness in young rabbits are likely due to prejunctional events with enhanced release of ACh. Increases in NGF and SP early in life may contribute to this increased responsiveness.

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Relaxation of guinea pig trachealis during electrical field stimulation increases with age

Cited by 25 publications

References 25 publications

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

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

Relaxation of tracheal smooth muscle is impaired in innate airway hyperresponsiveness

Mechanisms determining cholinergic neural responses in airways of young and mature rabbits

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