Effect of age on lung mechanics and airway reactivity in lambs

Sauder, Russell A.; McNicol, Kenneth J.; Stecenko, Arlene A.

doi:10.1152/jappl.1986.61.6.2074

Cited by 29 publications

(15 citation statements)

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“…Sensitivity to ACh increased with age, supporting the findings of other studies involving ovine airway smooth muscle (34,35). In vitro studies in several other mammalian species, however, have shown a decline in sensitivity during postnatal development to histamine (28,30,36), ACh (28), or a-adrenergic agents (29).…”

Section: Newbornsupporting

confidence: 82%

Maturational Changes in Airway Smooth Muscle Structure-Function Relationships

et al. 1992

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Section: Newbornsupporting

confidence: 82%

Maturational Changes in Airway Smooth Muscle Structure-Function Relationships

et al. 1992

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“…In man, airway responses to spasmogens such as methacholine have been demonstrated in infants less than 15 months of age (Tepper 1987). Similarly, in animal airways contractile responses to carbachol have been observed in foetal pigs at 95 days gestation (Sparrow and Mitchell 1990), in lambs aged 1 month (Sauder et al 1986) and in rabbits aged 3 days (Sanders and Grunstein 1983). In the present study, contractile responses were obtained to both acetylcholine and carbachol in guinea-pig isolated tracheal tissue from animals sacrificed at birth.…”

Section: Discussionmentioning

confidence: 93%

Age-related changes in muscarinic cholinoceptor function in guinea-pig and rat airways

Preuss

Goldie

1999

Naunyn-Schmiedeberg's Arch Pharmacol

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The influence of age on muscarinic cholinoceptor-mediated contraction and inositol phosphate accumulation was examined in rat and guinea-pig isolated tracheal tissue. Significant age-related changes in the sensitivity of guinea-pig tracheal tissue to acetylcholine, but not carbachol, were observed in the early maturation phase of growth with a 3.3-fold increase in potency between birth and 2 weeks of age followed by a 3.2-fold fall in potency between 2 and 12 weeks of age. Further ageing did not significantly change the potency of acetylcholine or carbachol. Whilst acetylcholinesterase inhibition caused a significant increase in acetylcholine potency, this was independent of animal age. In rat isolated tracheal tissue, contractile responses to both acetylcholine and carbachol remained unchanged with respect to animal age. Significant age-related decreases in inositol phosphate accumulation were observed in response to carbachol in the guinea-pig and rat and to acetylcholine in guinea-pig but not rat isolated tracheal tissue. This study has demonstrated significant age-related changes in the responsiveness of isolated tracheal tissue to carbachol and acetylcholine which were also species-specific.

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“…Although the reduction in lung volume in this group was not as consistent as in the other groups, this is an unlikely reason for the differences between the neonatal group and other groups. It is possible that neonatal ASM exhibits different responses to physical deformation, and, in addition, there is evidence of an ontogenic effect on airway responsiveness in sheep [33].…”

Section: Discussionmentioning

confidence: 99%

Low lung volume alters contractile properties of airway smooth muscle in sheep

McClean

Matheson²,

McKay³

et al. 2003

Eur Respir J

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Breathing at volumes lower than functional residual capacity (FRC) can induce changes in nonasthmatic airways consistent with the behaviour of asthmatic airways. This study investigated the chronic effect of breathing at volumes lower than FRC on the contractility of airway smooth muscle and myosin light chain kinase (MLCK) content and activity.Sheep of three age groups (neonate, adolescent and adult) had their FRC reduced by y25% for 4 weeks using a leather corset. Contractile responses to carbachol were then recorded in isolated tracheal strips and bronchial rings. MLCK content and activity were assessed by immunoblotting.The rate of stress generation increased in the bronchial smooth muscle of both adult and adolescent but not neonatal corseted sheep: adolescent corseted versus control, 65.0¡4.1 versus 103.4¡7.0 s (to reach 50% maximum stress), respectively; and adult corseted versus control, 57.0¡6.4 versus 93.4¡8.2 s, respectively. This was not due to increases in either bronchial or tracheal smooth muscle amount or MLCK content and activity.The present results indicate that chronic breathing at low lung volumes increases the rate of stress generation in airway smooth muscle. Excessive airway narrowing resulting from airway smooth muscle (ASM) contraction in response to physical and chemical stimuli is a characteristic of asthma. Breathing at volumes lower than functional residual capacity (FRC) can induce changes in nonasthmatic airways that are consistent with the behaviour of asthmatic airways. Animal studies have shown the marked influence of lung volume on ASM function [1][2][3], and in some clinical situations in which patients chronically breathe at lower lung volumes, this has been suggested as being responsible for changes in airway symptoms. This is the case in obese patients in whom there is an increased prevalence of wheezing [4-6] and airway hyperresponsiveness [7,8].The key regulator of the enzymatic pathway involved in smooth muscle contraction is myosin light chain kinase (MLCK), a dedicated protein kinase, with myosin as its only physiological substrate. MLCK regulates smooth muscle contraction by controlling the activity of actomyosin adenosine triphosphatase (ATPase) and in turn the rate of cross-bridge cycling [9,10]. In smooth muscle, it has been shown that the activity of actomyosin ATPase can be viewed mechanically as an index of shortening velocity [11,12]. A number of physiological studies have been performed using sensitised ASM as a model of asthmatic muscle. These studies have shown that sensitised ASM exhibits increased maximal shortening capacity and increased early shortening velocity [13,14]. Further investigations revealed that these observed changes in the contractile response of ASM were a result of an increase in both the amount and activity of MLCK present in the muscle [15][16][17].Another proposed mechanism for the effect of lung volume is ASM plasticity, in which the organisation of the contractile apparatus of the smooth muscle cell is modified to adapt to ...

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Effect of age on lung mechanics and airway reactivity in lambs

Cited by 29 publications

References 0 publications

Maturational Changes in Airway Smooth Muscle Structure-Function Relationships

Maturational Changes in Airway Smooth Muscle Structure-Function Relationships

Age-related changes in muscarinic cholinoceptor function in guinea-pig and rat airways

Low lung volume alters contractile properties of airway smooth muscle in sheep

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