Airway epithelium modulates the responsiveness of porcine bronchial smooth muscle

Stuart-Smith, K.; Vanhoutte, Paul M.

doi:10.1152/jappl.1988.65.2.721

Cited by 49 publications

(24 citation statements)

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“…A comparison of our results [this study] with those of Barnes et al [5] suggests that in airways of smaller caliber, the en hancing effect of epithelium removal is substantially re duced. These bovine data on epithelium modulation of muscle response are analogous with the pattern observed in airways of the canine respiratory tract [3] but different from those reported in the rabbit [2] and pig [4],…”

Section: Discussioncontrasting

confidence: 73%

Contraction of Bovine Isolated Bronchial Airways: Effects of Epithelium Removal

Ortiz

Labat²,

Norel³

et al. 1993

Respiration

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The influence of the epithelium on the contractile responses of bovine bronchial rings to acetylcholine, carbachol, 5-hydroxytryptamine and histamine was studied. Epithelium removal caused a significant leftward shift of the acetylcholine concentration-effect curve, pD₂ values were 2.86 ± 0.11 and 3.34 ± 0.18 for intact and rubbed tissue, respectively (P < 0.05). However, there was no change in the acetylcholine maximal response. The sensitivity and responsiveness of the bovine bronchus to the other spasmogens were not significantly altered by removal of the epithelium. These results suggest that the epithelium of bovine bronchi modulates only acetylcholine-induced contraction.

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Section: Discussioncontrasting

confidence: 73%

Contraction of Bovine Isolated Bronchial Airways: Effects of Epithelium Removal

Ortiz

Labat²,

Norel³

et al. 1993

Respiration

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“…The epithelium possesses one or more factors that are important for the relaxation of the underlying bronchial smooth muscle layer (3,51). Thus, removing the epithelium reduces isoproterenol relaxation in canine bronchi (51).…”

Section: Discussionmentioning

confidence: 99%

“…NS309; salbutamol; potassium; endothelium; GEA 3175 THE RESPIRATORY EPITHELIUM releases factors that regulate bronchial smooth muscle relaxations (20), and removal of the bronchial epithelium in larger airways has been shown to enhance the effect of contractile agonists and reduce the relaxing response in bronchioles (50,51). Nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) are mediators of human bronchiole smooth muscle epithelium-dependent relaxations (22).…”

mentioning

confidence: 99%

Mechanisms underlying epithelium-dependent relaxation in rat bronchioles: analogy to EDHF-type relaxation in rat pulmonary arteries

Kroigaard

Dalsgaard

Simonsen

2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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Kroigaard C, Dalsgaard T, Simonsen U. Mechanisms underlying epithelium-dependent relaxation in rat bronchioles: analogy to EDHFtype relaxation in rat pulmonary arteries. Am J Physiol Lung Cell Mol Physiol 298: L531-L542, 2010. First published January 29, 2010 doi:10.1152/ajplung.00220.2009.-This study investigated the mechanisms underlying epithelium-derived hyperpolarizing factor (EpDHF)-type relaxation in rat bronchioles. Immunohistochemistry was performed, and rat bronchioles and pulmonary arteries were mounted in microvascular myographs for functional studies. An opener of small (SKCa) and intermediate (IKCa)-conductance calcium-activated potassium channels, NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) was used to induce EpDHF-type relaxation. IK Ca and SKCa3 positive immunoreactions were observed mainly in the epithelium and endothelium of bronchioles and arteries, respectively. In 5-hydroxytryptamine (1 M)-contracted bronchioles (828 Ϯ 20 m, n ϭ 84) and U46619 (0.03 M)-contracted arteries (720 Ϯ 24 m, n ϭ 68), NS309 (0.001-10 M) induced concentration-dependent relaxations that were reduced by epithelium/endothelium removal and by blocking IK Ca channels with charybdotoxin and in bronchioles also by blocking SK Ca channels with apamin. Inhibition of cyclooxygenase, nitric oxide synthase, and cytochrome 2C isoenzymes, or blockade of large (BK Ca)-conductance calciumactivated potassium channels with iberiotoxin, failed to reduce NS309 relaxation. In contrast to the pulmonary arteries, relaxations to a ␤ 2-adrenoceptor agonist, salbutamol, were reduced in bronchioles by removing the epithelium or blocking IK Ca and/or SK Ca channels. Extracellular K ϩ (2-20 mM) induced relaxation in both bronchioles and arteries. An inhibitor of Na ϩ -K ϩ -ATPase, ouabain, abolished relaxations to NS309, salbutamol, and K ϩ . These results suggest that IK Ca and SKCa3 channels are located in the epithelium of bronchioles and endothelium of pulmonary arteries. Analog to the endotheliumderived hyperpolarizing factor (EDHF)-type relaxation in pulmonary arteries, these channels may be involved in EpDHF-type relaxation of bronchioles caused by epithelial K ϩ efflux followed by activation of Na ϩ -K ϩ -ATPase in the underlying smooth muscle layer.NS309; salbutamol; potassium; endothelium; GEA 3175 THE RESPIRATORY EPITHELIUM releases factors that regulate bronchial smooth muscle relaxations (20), and removal of the bronchial epithelium in larger airways has been shown to enhance the effect of contractile agonists and reduce the relaxing response in bronchioles (50, 51). Nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) are mediators of human bronchiole smooth muscle epithelium-dependent relaxations (22). In addition, a non-NO nonprostanoid epithelium-dependent hyperpolarizing factor (EpDHF) is also involved in epitheliumdependent relaxations. Epoxyeicosatrienoic acids (EETs) have been suggested to account for EpDHF-mediated relaxation in guinea pig airways (3). In comparison, opening of intermediate (IK Ca ) and endothelial subt...

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“…The epithelium is one potential source for such a substance [18][19][20][21], as are the subepithelial tissues [22]. Heterogeneous responses to ACh have been reported to occur in canine [20] and porcine [21] bronchial rings following epithelial removal, but this does not appear to be the case in perfused segments up to 3 mm in internal diameter [23].…”

Section: Discussionmentioning

confidence: 99%

Effect of diameter on force generation and responsiveness of bronchial segments and rings

Gray

Mitchell²

1996

Eur Respir J

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In this study, isovolumic bronchial segments and bronchial rings were used to investigate the influence of airway diameter on smooth muscle force generation and acetylcholine responsiveness.Segments with internal diameters ranging from 1.0-6.0 mm were obtained from the mainstem bronchus of eight pigs. Responses to increasing acetylcholine concentrations were quantified in segments by intralumenal pressure (cmH 2 O), and in rings by tension (g·cm -1 ). The negative log of the concentration producing half the maximal effect (EC50) (i.e. pD 2 ) to acetylcholine was calculated for each segment and ring. Ring tension was used to calculate a theoretical lumen pressure for each ring, and this, along with the pD 2 , was compared with values obtained from segments of the same diameter.Intermediate-sized segments produced significantly greater intralumenal pressures than did large or small segments. Small segments were 160 times more sensitive to acetylcholine than large segments. In contrast to the segments, bronchial rings showed no effect of size on acetylcholine sensitivity. Theoretical ring lumen pressures matched those measured for large and intermediate segments, but not for small segments.The different behaviour of bronchial segments and rings obtained from the same sized airway suggests that the three-dimensional architecture of the airway is an important factor in determining behaviour, particularly in small airways.

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Airway epithelium modulates the responsiveness of porcine bronchial smooth muscle

Cited by 49 publications

References 0 publications

Contraction of Bovine Isolated Bronchial Airways: Effects of Epithelium Removal

Contraction of Bovine Isolated Bronchial Airways: Effects of Epithelium Removal

Mechanisms underlying epithelium-dependent relaxation in rat bronchioles: analogy to EDHF-type relaxation in rat pulmonary arteries

Effect of diameter on force generation and responsiveness of bronchial segments and rings

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