Strain-related Differences in Airway Smooth Muscle and Airway Responsiveness in the Rat

Eidelman, David H.; Dimaria, G.; Bellofiore, S.; Wang, N. S.; Rd, Guttmann; Martin, James G.

doi:10.1164/ajrccm/144.4.792

Cited by 42 publications

(44 citation statements)

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“…The Fischer rats are well known to have greater responsiveness to contractile agonists, like MCh, compared with the Lewis rat in the absence of inflammation and without prior sensitization (11,19,46). Fischer airway smooth muscle has been characterized as having a greater rate of shortening ex vivo and in vitro (3,11). Our results also support these earlier findings: a MCh dose approximately threefold greater is required in the Lewis rats to achieve the same EC 200 R L as in the Fischer animals.…”

Section: The Fischer and Lewis Rat Model Of Airway Hyperresponsivenesssupporting

confidence: 86%

“…A greater level of LC 20 phosphorylation is also observed in the hyperresponsive Fischer rats. Along with previously reported factors, such as increased Ca 2ϩ mobilization (44) and increased smooth muscle mass (11) in the Fischer compared with the Lewis rat, these results suggest a genetically controlled mechanism by which multiple cellular and molecular functions are altered to produce an enhanced bronchoconstrictive response.…”

supporting

confidence: 82%

“…Aerosolized methacholine (MCh) dose-response curves on airway resistance were performed to verify the previously reported hyperresponsiveness of Fischer vs. Lewis rats (11,19,46). Pulmonary mechanics measurements were made in the spontaneously breathing animals using the Quadra-t system (SCIREQ; Montreal, PQ, Canada).…”

Section: Airway Responsiveness To Methacholinementioning

confidence: 99%

“…The highly inbred Fischer 344 and Lewis rat strains have been commonly used to investigate potential genetic determinants of innate airway hyperresponsiveness (11,19,46). The Fischer rats are well known to have greater responsiveness to contractile agonists, like MCh, compared with the Lewis rat in the absence of inflammation and without prior sensitization (11,19,46).…”

Section: The Fischer and Lewis Rat Model Of Airway Hyperresponsivenessmentioning

confidence: 99%

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Smooth muscle myosin isoform expression and LC₂₀phosphorylation in innate rat airway hyperresponsiveness

Gil¹,

Zitouni²,

Maghni³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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Four smooth muscle myosin heavy chain (SMMHC) isoforms are generated by alternative mRNA splicing of a single gene. Two of these isoforms differ by the presence [(ϩ)insert] or absence [(Ϫ)insert] of a 7-amino acid insert in the motor domain. The rate of actin filament propulsion of the (ϩ)insert SMMHC isoform, as measured in the in vitro motility assay, is twofold greater than that of the (Ϫ)insert isoform. We hypothesized that a greater expression of the (ϩ)insert SMMHC isoform and greater regulatory light chain (LC 20) phosphorylation contribute to airway hyperresponsiveness. We measured airway responsiveness to methacholine in Fischer hyperresponsive and Lewis normoresponsive rats and determined SMMHC isoform mRNA and protein expression, as well as essential light chain (LC 17) isoforms, h-caldesmon, and ␣-actin protein expression in their tracheae. We also measured tracheal muscle strip contractility in response to methacholine and corresponding LC 20 phosphorylation. We found Fischer rats have more (ϩ)insert mRNA (69.4 Ϯ 2.0%) (mean Ϯ SE) than Lewis rats (53.0 Ϯ 2.4%; P Ͻ 0.05) and a 44% greater content of (ϩ)insert isoform relative to total myosin protein. No difference was found for LC 17 isoform, h-caldesmon, and ␣-actin expression. The contractility experiments revealed a greater isometric force for Fischer trachealis segments (4.2 Ϯ 0.8 mN) than Lewis (1.9 Ϯ 0.4 mN; P Ͻ 0.05) and greater LC 20 phosphorylation level in Fischer (55.1 Ϯ 6.4) than in Lewis (41.4 Ϯ 6.1; P Ͻ 0.05) rats. These results further support the contention that innate airway hyperresponsiveness is a multifactorial disorder in which increased expression of the fast (ϩ)insert SMMHC isoform and greater activation of LC20 lead to smooth muscle hypercontractility. myosin heavy chain; 7-amino acid insert; phasic muscle; tonic muscle; myosin regulatory light chain; trachealis

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Section: The Fischer and Lewis Rat Model Of Airway Hyperresponsivenesssupporting

confidence: 86%

supporting

confidence: 82%

Section: Airway Responsiveness To Methacholinementioning

confidence: 99%

Section: The Fischer and Lewis Rat Model Of Airway Hyperresponsivenessmentioning

confidence: 99%

See 2 more Smart Citations

Smooth muscle myosin isoform expression and LC₂₀phosphorylation in innate rat airway hyperresponsiveness

Gil¹,

Zitouni²,

Maghni³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…in open-chest condition (12,(15)(16)(17), which is not representative of the conditions in the pediatric respiratory function laboratory. Airway responsiveness to Mch has been shown in the Brown Norway rat (18,19), and there are few data on how respiratory mechanics may be affected by the occurrence of DI in that model. The aim of the study was therefore to describe the effects of DI in closed chest Brown Norway rats challenged with Mch.…”

mentioning

confidence: 99%

Deep Inhalation Prevents the Respiratory Elastance Response to Methacholine in Rats

et al. 2006

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ABSTRACT:The bronchodilator effect of deep inhalation (DI) may be assessed from the time course of respiratory system resistance (Rrs) and reactance (Xrs) measured by the forced oscillation technique at a single frequency. The aim of the study was to assess the effect of DI in the closed chest rat. Under anesthesia and mechanical ventilation, seven Brown Norway rats were given regular DI (BN-di) and six underwent continuous tidal ventilation (BN) throughout an otherwise similar methacholine (Mch) challenge protocol. Rrs and Xrs were monitored at 20 Hz and apparent respiratory system elastance (Ers) was computed from Xrs. After Mch nebulization, there was a significant increase in Rrs and Ers compared with saline. Ers, but not Rrs, decreased after the DI and BN-di were found to have lower Ers than BN. Thus, DI significantly alters Ers and its response to Mch. Computer simulations suggested reversal of increased viscoelasticity and/or inhomogeneous behavior by the DI in that model. R ecent technological progress has promoted a number of methods for the study of respiratory function in subjects that show little cooperation capability. The forced oscillation technique is used in young children to measure the mechanical impedance of the respiratory system (Zrs). An externally generated periodic flow of small amplitude is delivered at the airway opening. Excitation frequencies may range from very low (Ͻ0.5 Hz) to very high (Ͼ50 Hz). In routine pediatric practice, however, the operating range is narrower. The use of very low frequencies is limited by the breathing of the subject and the upper airway wall motion is responsible for significant artefact at higher frequencies (1,2). As a result, most of the relevant information on respiratory mechanical properties in children so far appear to have been obtained somewhere between 5 and 15 Hz (3). The use of a single excitation frequency allows tracking Zrs changes during breathing (4 -6), which is of particular interest in view of the significant time-dependent alteration in airway function that may be observed after a deep inhalation (DI) (7,8). A decrease in airway resistance after a DI is thus highly suggestive of reversal of bronchoconstriction (9 -12). Therefore, the airway response to a DI has the capability of assessing the mechanisms of airway obstruction and has recently been applied to the study of airway hyperresponsiveness in children using the forced oscillation technique (5,13,14).Whole animal experiments are potentially useful to assess mechanisms through which a DI acts on the airways and to contribute to validating the techniques used in the routine lung function laboratory. Most studies in experimental animals are performed on lung mechanics, i.e. in open-chest condition (12,15-17), which is not representative of the conditions in the pediatric respiratory function laboratory. Airway responsiveness to Mch has been shown in the Brown Norway rat (18,19), and there are few data on how respiratory mechanics may be affected by the occurrence of DI in that model...

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Environmental effects on pulmonary mechanics and the response to inhaled methacholine

Sly¹,

Willet²,

Habre³

1998

Pediatr. Pulmonol.

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Strain-related Differences in Airway Smooth Muscle and Airway Responsiveness in the Rat

Cited by 42 publications

References 1 publication

Smooth muscle myosin isoform expression and LC₂₀phosphorylation in innate rat airway hyperresponsiveness

Smooth muscle myosin isoform expression and LC₂₀phosphorylation in innate rat airway hyperresponsiveness

Deep Inhalation Prevents the Respiratory Elastance Response to Methacholine in Rats

Environmental effects on pulmonary mechanics and the response to inhaled methacholine

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Strain-related Differences in Airway Smooth Muscle and Airway Responsiveness in the Rat

Cited by 42 publications

References 1 publication

Smooth muscle myosin isoform expression and LC20phosphorylation in innate rat airway hyperresponsiveness

Smooth muscle myosin isoform expression and LC20phosphorylation in innate rat airway hyperresponsiveness

Deep Inhalation Prevents the Respiratory Elastance Response to Methacholine in Rats

Environmental effects on pulmonary mechanics and the response to inhaled methacholine

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Product

Resources

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Smooth muscle myosin isoform expression and LC₂₀phosphorylation in innate rat airway hyperresponsiveness

Smooth muscle myosin isoform expression and LC₂₀phosphorylation in innate rat airway hyperresponsiveness