scholarly journals Dynamic equilibration of airway smooth muscle contraction during physiological loading

2002 ◽  
Vol 92 (2) ◽  
pp. 771-779 ◽  
Author(s):  
Jeanne Latourelle ◽  
Ben Fabry ◽  
Jeffrey J. Fredberg
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Experimental Method ◽  
Airway Smooth Muscle ◽  
Muscle Length ◽  
Transpulmonary Pressure ◽  
Smooth Muscle Contraction ◽  
Control Force ◽  
Airway Narrowing

Airway smooth muscle contraction is the central event in acute airway narrowing in asthma. Most studies of isolated muscle have focused on statically equilibrated contractile states that arise from isometric or isotonic contractions. It has recently been established, however, that muscle length is determined by a dynamically equilibrated state of the muscle in which small tidal stretches associated with the ongoing action of breathing act to perturb the binding of myosin to actin. To further investigate this phenomenon, we describe in this report an experimental method for subjecting isolated muscle to a dynamic microenvironment designed to closely approximate that experienced in vivo. Unlike previous methods that used either time-varying length control, force control, or time-invariant auxotonic loads, this method uses transpulmonary pressure as the controlled variable, with both muscle force and muscle length free to adjust as they would in vivo. The method was implemented by using a servo-controlled lever arm to load activated airway smooth muscle strips with transpulmonary pressure fluctuations of increasing amplitude, simulating the action of breathing. The results are not consistent with classical ideas of airway narrowing, which rest on the assumption of a statically equilibrated contractile state; they are consistent, however, with the theory of perturbed equilibria of myosin binding. This experimental method will allow for quantitative experimental evaluation of factors that were previously outside of experimental control, including sensitivity of muscle length to changes of tidal volume, changes of lung volume, shape of the load characteristic, loss of parenchymal support and inflammatory thickening of airway wall compartments.

Blockade of eosinophil migration by 5-lipoxygenase and cyclooxygenase inhibition in explanted guinea pig trachealis

1995 ◽  
Vol 268 (3) ◽  
pp. L446-L454 ◽  
Author(s):  
N. M. Munoz ◽  
A. R. Leff
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Muscle Contraction ◽  
Airway Smooth Muscle ◽  
Smooth Muscle Contraction ◽  
Cyclooxygenase Inhibition ◽  
Airway Narrowing ◽  
Eosinophil Migration ◽  
Eosinophil Chemotaxis ◽  
Physical Consequences

We studied the effects of 5-lipoxygenase inhibition with A63162 and cyclooxygenase inhibition with indomethacin (INDO) on 1) eosinophil chemotaxis and 2) airway narrowing caused by 10(-6) M formyl-Met-Leu-Phe (fMLP) in tracheal explants from guinea pigs. Airway narrowing was assessed by calibrated micrometry, and eosinophil migration from the lamina propria was expressed as number of eosinophils contained per 1 cm tracheal segment. After 120 min, treatment with fMLP caused an increase in luminal eosinophils from 6,804 +/- 1,786 to 303,347 +/- 75,609 cells (P < 0.001); airway diameter narrowed by 20.4 +/- 1.4%. In six preparations, A63162 inhibited airway narrowing caused by fMLP by 54.9 +/- 6.1%; INDO had a similar effect on airway diameter. However, maximal inhibition of eosinophil migration was greater after 10(-6) M A63162 (38,393 +/- 7,434 cells; P < 0.001 vs. fMLP alone) than after treatment with 10(-5) M INDO (123,547 +/- 19,499 cells; P < 0.05). We demonstrate a method that permits simultaneous measurements of eosinophil migration and airway smooth muscle contraction in a guinea pig tracheal explant preparation. Our data suggest that eosinophil chemotaxis and changes in internal airway diameter are caused by activation of both 5-lipoxygenase and cyclooxygenase pathways and that cell migration is independent of the physical consequences of airway smooth muscle contraction.

ET-1-induced bronchoconstriction is mediated via ETB receptor in mice

1997 ◽  
Vol 83 (1) ◽  
pp. 46-51 ◽  
Author(s):  
Takahide Nagase ◽  
Tomoko Aoki ◽  
Teruaki Oka ◽  
Yoshinosuke Fukuchi ◽  
Yasuyoshi Ouchi
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Function ◽  
Airway Smooth Muscle ◽  
Smooth Muscle Contraction ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Airway Narrowing ◽  
Wall Area ◽  
Significant Difference

Nagase, Takahide, Tomoko Aoki, Teruaki Oka, Yoshinosuke Fukuchi, and Yasuyoshi Ouchi. ET-1-induced bronchoconstriction is mediated via ETB receptor in mice. J. Appl. Physiol. 83(1): 46–51, 1997.—Endothelin (ET)-1 is one of the most potent agonists of airway smooth muscle and can act via two different ET receptor subtypes, i.e., ETA and ETB. To determine the effects of ET-1 on in vivo pulmonary function and which ET receptors are involved in murine lungs, we investigated 1) the effects of ET and sarafotoxin S6c (S6c), a selective ETB agonist, on pulmonary function and 2) the effects of BQ-123 and BQ-788, specific ETA- and ETB-receptor antagonists, on ET-1-induced bronchoconstriction. ICR mice were anesthetized and mechanically ventilated (frequency = 2.5 Hz, tidal volume = 8 ml/kg, positive end-expiratory pressure = 3 cmH2O). Intravenous ET-1, ET-2, and ET-3 increased lung resistance similarly and equipotently, whereas S6c elicited a greater degree of bronchoconstriction. Mice were then pretreated with saline (Sal), BQ-123 (0.2, 1, and 5 mg/kg), or BQ-788 (0.2, 1, and 5 mg/kg) before administration of ET-1 (10−7 mol/kg iv). No dose of BQ-123 blocked ET-1-induced constriction, whereas pretreatment with each dose of BQ-788 significantly inhibited ET-1-induced responses. There were significant differences in morphometrically assessed airway constriction between Sal and BQ-788 and between BQ-123 and BQ-788, whereas no significant difference was observed between Sal and BQ-123. There were no significant morphometric differences in the airway wall area among the three groups. These observations suggest that the ETB- but not ETA-receptor subtype may mediate the changes in murine pulmonary function in response to ET-1. In addition, the ETB-receptor antagonist reduces ET-1-induced airway narrowing by affecting airway smooth muscle contraction in mice.

Models to study airway smooth muscle contraction in vivo, ex vivo and in vitro: Implications in understanding asthma

2013 ◽  
Vol 26 (1) ◽  
pp. 24-36 ◽  
Author(s):  
David Wright ◽  
Pawan Sharma ◽  
Min-Hyung Ryu ◽  
Paul-Andre Rissé ◽  
Melanie Ngo ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Airway Smooth Muscle ◽  
Ex Vivo ◽  
Smooth Muscle Contraction

scholarly journals The mechanics of the lung parenchyma and airway responsiveness to metacholine

2004 ◽  
Vol 61 (4) ◽  
Author(s):  
F.G. Salerno ◽  
O. Resta ◽  
M.P. Foschino-Barbaro ◽  
A. Spanevello
Keyword(s):  
Mechanical Properties ◽  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Muscle Contraction ◽  
Airway Smooth Muscle ◽  
Muscle Activation ◽  
Mechanical Load ◽  
Lung Parenchyma ◽  
Smooth Muscle Contraction ◽  
Airway Narrowing

The lung parenchyma is anatomically and mechanically connected to the intraparenchymal airways. Due to forces of interdependence the lung parenchyma represents a mechanical load that opposes bronchial narrowing during airway smooth muscle activation. The mechanical load caused by the parenchyma is a function of the number of the alveolar attachments to the airways, and of the mechanical properties of the parenchyma. The extracellular matrix is a major component of the lung parenchyma responsible of most of its mechanical properties. The excessive airway narrowing observed in the asthmatic population may be the consequence of the altered mechanical properties of the extracellular matrix reducing the mechanical load that opposes airway smooth muscle contraction.

Effect of time-varying load on degree of bronchoconstriction in the dog

1998 ◽  
Vol 85 (4) ◽  
pp. 1464-1470 ◽  
Author(s):  
Norihiro Shinozuka ◽  
Jean-Pierre Lavoie ◽  
James G. Martin ◽  
Jason H. T. Bates
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Airway Smooth Muscle ◽  
Lung Volume ◽  
In Vitro Study ◽  
Smooth Muscle Contraction ◽  
Lung Mechanics ◽  
Muscle Shortening

It is well established that the degree of airway smooth muscle shortening produced by a given dose of bronchial agonist is greatly affected by lung volume. The airways are tethered by parenchymal attachments, the tension of which increases progressively with lung volume, thereby presenting a commensurately increasing hindrance to smooth muscle contraction. Earlier studies (P. F. Dillon, M. O. Aksoy, S. P. Driska, and R. A. Murphy. Science 211: 495–497, 1981) presented evidence that smooth muscle contraction initially involves rapidly cycling cross bridges, which then change to noncycling (latch) bridges. They also suggested that most of the muscle shortening occurs during the early rapid cross-bridge phase. This implies that smooth muscle subject to a given load early in contraction should shorten less than when it is subject to the same load later on. An in vitro study (W. Li and N. L. Stephens. Can. J. Physiol. Pharmacol. 72: 1458–1463, 1994) obtained support for this notion. To test this hypothesis in vivo, we measured the changes in lung impedance at 1 and 6 Hz produced in dogs by a bolus intravenous injection of methacholine when lung volume was increased for 10 s at different times after injection. We found that the changes in mechanics were greatly inhibited, whereas lung volume was elevated. However, when lung volume was returned to its initial level, the lung mechanics continued to change at a rate unaffected by the preceding volume change. We conclude that temporary mechanical inhibition of airway smooth muscle shortening in the normal dog in vivo merely delays an otherwise normal course of contraction.

Phosphorylation of dense-plaque proteins talin and paxillin during tracheal smooth muscle contraction

1995 ◽  
Vol 268 (3) ◽  
pp. C563-C571 ◽  
Author(s):  
F. M. Pavalko ◽  
L. P. Adam ◽  
M. F. Wu ◽  
T. L. Walker ◽  
S. J. Gunst
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Airway Smooth Muscle ◽  
Fold Increase ◽  
Smooth Muscle Contraction ◽  
Tracheal Smooth Muscle ◽  
Airway Smooth Muscle Cells ◽  
Attachment Proteins ◽  
Phosphopeptide Mapping

Reorganization of cytoskeletal-membrane interactions during contractile stimulation may contribute to the regulation of airway smooth muscle contraction. We investigated the effect of contractile stimulation on the phosphorylation of the actin-membrane attachment proteins talin, vinculin, and paxillin. Stimulation of 32P-labeled canine tracheal smooth muscle strips with acetylcholine (ACh; 10(-3) M) resulted in a rapid 2.6-fold increase in phosphorylation of serine and/or threonine residues, compared with resting levels of 0.22 mol PO4(3-)/mol talin. After stimulation with ACh, phosphorylation of tyrosine residues on paxillin increased approximately threefold. Two-dimensional phosphopeptide mapping of in vivo labeled talin and paxillin indicated phosphorylation on a limited number of sites. Vinculin phosphorylation was undetectable in either resting or ACh-stimulated muscle. We conclude that phosphorylation of talin and paxillin occurs during ACh-stimulated contraction of tracheal smooth muscle and that distinct signaling pathways activate a serine/threonine kinase that phosphorylates talin and a tyrosine kinase that phosphorylates paxillin. The pharmacological activation of airway smooth muscle cells might involve the anchoring of contractile filaments to the membrane.

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