Cyclical elongation regulates contractile responses of isolated airways

Abstract

.-Bronchoconstrictor responses are quantitatively different when they are evoked under static conditions and during or after periods of deep inspiration. In vivo, deep inspirations produce bronchodilation and protect the lung from subsequent bronchoconstriction (termed bronchoprotection). These effects may be due in part to dynamic stretch on airways produced by cyclical expansion of airway diameter. However, airways also lengthen cyclically during breathing. The effects of cyclical airway elongation on evoked bronchoconstriction have not been examined. This study recorded evoked contractions of pig bronchial segments 1) at different airway lengths, 2) after a period of cyclical lengthening in relaxed airways, and 3) during cyclical lengthening in pretoned airways. Airway segments were mounted in organ baths and bathed in Krebs solution luminally and on the adventitia. Airways were cyclically lengthened by 5-30% of their deflated length at 0.5-2 Hz for 5 min. Contractions were evoked by electrical field stimulation or carbachol and were recorded under isovolumic conditions. Under static conditions, there was a blunt relationship between length and response to electrical field stimulation. After a period of airway length cycling, electrical field stimulation-induced contractions were increased. In airways pretoned with carbachol, cyclical lengthening produced a transient bronchodilation and a sustained increase in contraction. Contractile responses were not blocked by indomethacin. The results show that isolated airways respond actively to dynamic changes in length. Our results indicate that cyclical lengthening of airways could contribute to lung function in vivo but does not appear to account for the phenomenon of bronchoprotection.bronchoconstriction; airway smooth muscle; deep inspiration LUNG VOLUME HAS A NUMBER of different effects on the capacity of airways to actively narrow. Under static or semistatic conditions, evoked bronchoconstriction is reduced at high lung volumes as a result of increased afterload on airway smooth muscle (ASM) (16,17). Conversely, at low lung volumes, bronchoconstriction is enhanced. Under conditions present during normal breathing or deep inspirations (DI), the respiratory system responds actively to the dynamic conditions present. For example, in normal subjects, periods of DI produced bronchodilation and, importantly, reduced bronchoconstriction that was evoked subsequently to the DI (5,14,18,22,24,28). The latter phenomenon has been termed bronchoprotection. Some authors (6) propose that bronchoprotection is one of the most powerful protectective mechanisms in the airway. Bronchoprotection has added significance because the phenomenon appears to be lost or even reversed in subjects with asthma (14, 24).The causes of bronchodilation and bronchoprotection are not fully understood but may involve the effects of cyclical force on ASM (6, 34, 36). With normal tidal breaths and DI, airways expand in diameter and also elongate (1, 12, 19). The effects of cyclical expansion on airway...

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

“…WANG et al [69] found that periodic stretching of isolated porcine ASM in the relaxed state resulted in a decrease of force production with subsequent contractions. However, pressure oscillation in isolated airway segments that periodically strained the ASM embedded within the segment led to a slight increase of the pressure generated in the subsequent isovolumic ''constriction'' [295,296]. Airways were subjected to either radial [295] or axial [296] distension, with similar findings.…”

“…However, pressure oscillation in isolated airway segments that periodically strained the ASM embedded within the segment led to a slight increase of the pressure generated in the subsequent isovolumic ''constriction'' [295,296]. Airways were subjected to either radial [295] or axial [296] distension, with similar findings. Radial strain increased ASM length, whereas under the experimental conditions applied, axial distension reduced ASM length.…”

“…In vitro studies on the behaviour of isolated pig airway segments also produced results not predicted by the behaviour of isolated ASM [295,296]. WANG et al [69] found that periodic stretching of isolated porcine ASM in the relaxed state resulted in a decrease of force production with subsequent contractions.…”

“…Discrepancies in findings from airway segments and ASM So far, there is no clear explanation as to why periodic stretches applied, by pressure oscillation, to ASM embedded in intact airways increase muscle contractility, and why stretches applied to isolated ASM bundles have an opposite effect [295,296]. This question needs to be answered before any interpretation of stretch-induced alteration in ASM properties in terms of lung function can be taken seriously.…”

Involvement of the Neurokinin-2 Receptor in Airway Smooth Muscle Stretch-Activated Contractions Assessed in Perfused Intact Bovine Bronchial Segments

“…After the dissection and excision of the bronchial segment, side branches were tightly ligated with surgical silk (4-0) as previously mentioned (Mitchell et al, 1998;Khangure et al, 2004). The ligated bronchial segment was then mounted horizontally in a 30-ml Mayflower organ bath (Hugo Sachs Elektronik-Harvard Apparatus GmbH, March-Hugstetten, Germany) containing warmed modified Krebs buffer solution (37°C) gassed with carbogen (95% O 2 -5% CO 2 ) as previously mentioned by Mitchell and Sparrow (1994) with modifications.…”