Mechanisms for the mechanical response of airway smooth muscle to length oscillation

1997 ◽  
Vol 83 (3) ◽  
pp. 731-738 ◽  
Author(s):  
X. Shen ◽  
M. F. Wu ◽  
R. S. Tepper ◽  
S. J. Gunst
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Mechanical Response ◽  
Muscle Tone ◽  
Isometric Force ◽  
Muscle Length ◽  
Contractile Element ◽  
Active Force ◽  
Cross Bridge

Shen, X., M. F. Wu, R. S. Tepper, and S. J. Gunst. Mechanisms for the mechanical response of airway smooth muscle to length oscillation. J. Appl. Physiol. 83(3): 731–738, 1997.—Airway smooth muscle tone in vitro is profoundly affected by oscillations in muscle length, suggesting that the effects of lung volume changes on airway tone result from direct effects of stretch on the airway smooth muscle. We analyzed the effect of length oscillation on active force and length-force hysteresis in canine tracheal smooth muscle at different oscillation rates and amplitudes during contraction with acetylcholine. During the shortening phase of the length oscillation cycle, the active force generated by the smooth muscle decreased markedly below the isometric force but returned to isometric force as the muscle was lengthened. Results indicate that at rates comparable to those during tidal breathing, active shortening and yielding of contractile elements contributes to the modulation of force during length oscillation; however, the depression of force during shortening cannot be accounted for by cross-bridge properties, shortening-induced cross-bridge deactivation, or active relaxation. We conclude that the depression of contractility may be a function of the plasticity of the cellular organization of contractile filaments, which enables contractile element length to be reset in relation to smooth muscle cell length as a result of smooth muscle stretch.

scholarly journals Could an increase in airway smooth muscle shortening velocity cause airway hyperresponsiveness?

2011 ◽  
Vol 300 (1) ◽  
pp. L121-L131 ◽  
Author(s):  
Sharon R. Bullimore ◽  
Sana Siddiqui ◽  
Graham M. Donovan ◽  
James G. Martin ◽  
James Sneyd ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Isometric Force ◽  
Muscle Length ◽  
Shortening Velocity ◽  
Bridge Model ◽  
Generating Capacity ◽  
Cross Bridges

Airway hyperresponsiveness (AHR) is a characteristic feature of asthma. It has been proposed that an increase in the shortening velocity of airway smooth muscle (ASM) could contribute to AHR. To address this possibility, we tested whether an increase in the isotonic shortening velocity of ASM is associated with an increase in the rate and total amount of shortening when ASM is subjected to an oscillating load, as occurs during breathing. Experiments were performed in vitro using 27 rat tracheal ASM strips supramaximally stimulated with methacholine. Isotonic velocity at 20% isometric force (Fiso) was measured, and then the load on the muscle was varied sinusoidally (0.33 ± 0.25 Fiso, 1.2 Hz) for 20 min, while muscle length was measured. A large amplitude oscillation was applied every 4 min to simulate a deep breath. We found that: 1) ASM strips with a higher isotonic velocity shortened more quickly during the force oscillations, both initially ( P < 0.001) and after the simulated deep breaths ( P = 0.002); 2) ASM strips with a higher isotonic velocity exhibited a greater total shortening during the force oscillation protocol ( P < 0.005); and 3) the effect of an increase in isotonic velocity was at least comparable in magnitude to the effect of a proportional increase in ASM force-generating capacity. A cross-bridge model showed that an increase in the total amount of shortening with increased isotonic velocity could be explained by a change in either the cycling rate of phosphorylated cross bridges or the rate of myosin light chain phosphorylation. We conclude that, if asthma involves an increase in ASM velocity, this could be an important factor in the associated AHR.

Inhibition of dihydropyridine-sensitive calcium entry in hypoxic relaxation of airway smooth muscle

1995 ◽  
Vol 268 (2) ◽  
pp. L201-L206 ◽  
Author(s):  
C. Vannier ◽  
T. L. Croxton ◽  
L. S. Farley ◽  
C. A. Hirshman
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Bay K 8644 ◽  
O2 Concentration ◽  
Voltage Dependent ◽  
Progressive Hypoxia ◽  
Carbamyl Choline

Hypoxia dilates airways in vivo and reduces active tension of airway smooth muscle in vitro. To determine whether hypoxia impairs Ca2+ entry through voltage-dependent channels (VDC), we tested the ability of dihydropyridines to modulate hypoxia-induced relaxation of KCl- and carbamyl choline (carbachol)-contracted porcine bronchi. Carbachol- or KCl-contracted bronchial rings were exposed to progressive hypoxia in the presence or absence of 1 microM BAY K 8644 (an L-type-channel agonist). In separate experiments, rings were contracted with carbachol or KCl, treated with nifedipine (a VDC antagonist), and finally exposed to hypoxia. BAY K 8644 prevented hypoxia-induced relaxation in KCl-contracted bronchi. Nifedipine (10(-5) M) totally relaxed KCl- contracted bronchi. Carbachol-contracted bronchi were only partially relaxed by nifedipine but were completely relaxed when the O2 concentration of the gas was reduced from 95 to 0%. These data indicate that hypoxia can reduce airway smooth muscle tone by limiting entry of Ca2+ through a dihydropyridine-sensitive pathway, but that other mechanisms also contribute to hypoxia-induced relaxation of carbachol-contracted bronchi.

scholarly journals Series-to-parallel transition in the filament lattice of airway smooth muscle

2000 ◽  
Vol 89 (3) ◽  
pp. 869-876 ◽  
Author(s):  
Chun Y. Seow ◽  
Victor R. Pratusevich ◽  
Lincoln E. Ford
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Length ◽  
Thick Filament ◽  
Cycling Rate ◽  
Cross Bridge ◽  
Parallel Change ◽  
Force Velocity ◽  
Cross Bridges ◽  
Trachealis Muscle

Force-velocity curves measured at different times during tetani of sheep trachealis muscle were analyzed to assess whether velocity slowing could be explained by thick-filament lengthening. Such lengthening increases force by placing more cross bridges in parallel on longer filaments and decreases velocity by reducing the number of filaments spanning muscle length. From 2 s after the onset of stimulation, when force had achieved 42% of it final value, to 28 s, when force had been at its tetanic plateau for ∼15 s, velocity decreases were exactly matched by force increases when force was adjusted for changes in activation, as assessed from the maximum power value in the force-velocity curves. A twofold change in velocity could be quantitatively explained by a series-to-parallel change in the filament lattice without any need to postulate a change in cross-bridge cycling rate.

In vivo loads on airway smooth muscle: the role of noncontractile airway structures

1992 ◽  
Vol 70 (4) ◽  
pp. 602-606 ◽  
Author(s):  
Philip Robinson ◽  
Mitsushi Okazawa ◽  
Tony Bai ◽  
Peter Paré
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Activation ◽  
Muscle Length ◽  
Tracheal Cartilage ◽  
Elastic Load ◽  
Muscle Shortening ◽  
Trachealis Muscle

The degree of airway smooth muscle contraction and shortening that occurs in vivo is modified by many factors, including those that influence the degree of muscle activation, the resting muscle length, and the loads against which the muscle contracts. Canine trachealis muscle will shorten up to 70% of starting length from optimal length in vitro but will only shorten by around 30% in vivo. This limitation of shortening may be a result of the muscle shortening against an elastic load such as could be applied by tracheal cartilage. Limitation of airway smooth muscle shortening in smaller airways may be the result of contraction against an elastic load, such as could be applied by lung parenchymal recoil. Measurement of the elastic loads applied by the tracheal cartilage to the trachealis muscle and by lung parenchymal recoil to smooth muscle of smaller airways were performed in canine preparations. In both experiments the calculated elastic loads applied by the cartilage and the parenchymal recoil explained in part the limitation of maximal active shortening and airway narrowing observed. We conclude that the elastic loads provided by surrounding structures are important in determining the degree of airway smooth muscle shortening and the resultant airway narrowing.Key words: elastic loads, tracheal cartilage, airway smooth muscle shortening.

Airway smooth muscle tone increases airway responsiveness in healthy young adults

2017 ◽  
Vol 312 (3) ◽  
pp. L348-L357 ◽  
Author(s):  
Morgan Gazzola ◽  
Katherine Lortie ◽  
Cyndi Henry ◽  
Samuel Mailhot-Larouche ◽  
David G. Chapman ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Airway Responsiveness ◽  
High Dose ◽  
Forced Oscillation Technique ◽  
Single High Dose ◽  
Healthy Humans

Force adaptation, a process whereby sustained spasmogenic activation (viz., tone) of airway smooth muscle (ASM) increases its contractile capacity, has been reported in isolated ASM tissues in vitro, as well as in mice in vivo. The objective of the present study was to assess the effect of tone on airway responsiveness in humans. Ten healthy volunteers underwent methacholine challenge on two occasions. One challenge consisted of six serial doses of saline followed by a single high dose of methacholine. The other consisted of six low doses of methacholine 5 min apart followed by a higher dose. The cumulative dose was identical for both challenges. After both methacholine challenges, subjects took a deep inspiration (DI) to total lung capacity as another way to probe ASM mechanics. Responses to methacholine and the DI were measured using a multifrequency forced oscillation technique. Compared with a single high dose, the challenge preceded by tone led to an elevated response measured by respiratory system resistance (Rrs) and reactance at 5 Hz. However, there was no difference in the increase in Rrs at 19 Hz, suggesting a predominant effect on smaller airways. Increased tone also reduced the efficacy of DI, measured by an attenuated maximal dilation during the DI and an increased renarrowing post-DI. We conclude that ASM tone increases small airway responsiveness to inhaled methacholine and reduces the effectiveness of DI in healthy humans. This suggests that force adaptation may contribute to airway hyperresponsiveness and the reduced bronchodilatory effect of DI in asthma.

Tissue elastance influences airway smooth muscle shortening: comparison of mechanical properties among different species

2002 ◽  
Vol 80 (9) ◽  
pp. 865-871 ◽  
Author(s):  
Anabelle M. Opazo Saez ◽  
R Robert Schellenberg ◽  
Mara S Ludwig ◽  
Richard A Meiss ◽  
Peter D Paré
Keyword(s):  
Mechanical Properties ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Isometric Force ◽  
Published Data ◽  
Passive Tension ◽  
Active Force ◽  
Muscle Shortening ◽  
Human Airways ◽  
Tissue Elastance

We have observed striking differences in the mechanical properties of airway smooth muscle preparations among different species. In this study, we provide a novel analysis on the influence of tissue elastance on smooth muscle shortening using previously published data from our laboratory. We have found that isolated human airways exhibit substantial passive tension in contrast to airways from the dog and pig, which exhibit little passive tension (<5% of maximal active force versus ~60% for human bronchi). In the dog and pig, airway preparations shorten up to 70% from Lmax (the length at which maximal active force occurs), whereas human airways shorten by only ~12% from Lmax. Isolated airways from the rabbit exhibit relatively low passive tension (~22% Fmax) and shorten by 60% from Lmax. Morphologic evaluation of airway cross sections revealed that 25-35% of the airway wall is muscle in canine, porcine, and rabbit airways in contrast to ~9% in human airway preparations. We postulate that the large passive tension needed to stretch the muscle to Lmax reflects the high connective tissue content surrounding the smooth muscle, which limits shortening during smooth muscle contraction by imposing an elastic load, as well as by causing radial constraint.Key words: isometric force, isotonic shortening, elastance.

scholarly journals Modeling the impairment of airway smooth muscle force by stretch

2015 ◽  
Vol 118 (6) ◽  
pp. 684-691 ◽  
Author(s):  
Jason H. T. Bates
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Coarse Grained ◽  
Active Force ◽  
Cross Bridge ◽  
Bulk Force ◽  
Length Changes ◽  
Cross Bridges ◽  
Large Stretch ◽  
Two State Model

Imposed length changes of only a small percent produce transient reductions in active force in strips of airway smooth muscle (ASM) due to the temporary detachment of bound cross-bridges caused by the relative motion of the actin and myosin fibers. More dramatic and sustained reductions in active force occur following large changes in length. The Huxley two-state model of skeletal muscle originally proposed in 1957 and later adapted to include a four-state description of cross-bridge kinetics has been widely used to model the former phenomenon, but is unable to account for the latter unless modified to include mechanisms by which the contractile machinery in the ASM cell becomes appropriately rearranged. Even so, the Huxley model itself is based on the assumption that the contractile proteins are all aligned precisely in the direction of bulk force generation, which is not true for ASM. The present study derives a coarse-grained version of the Huxley model that is free of inherent assumptions about cross-bridge orientation. This simplified model recapitulates the key features observed in the force-length behavior of activated strips of ASM and, in addition, provides a mechanistically based way of accounting for the sustained force reductions that occur following large stretch.

Relaxation of activated airway smooth muscle: relative potency of isoproterenol vs. tidal stretch

2001 ◽  
Vol 90 (6) ◽  
pp. 2306-2310 ◽  
Author(s):  
Alison Gump ◽  
Laura Haughney ◽  
Jeffrey Fredberg
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Signal Transduction Pathway ◽  
Muscle Length ◽  
Active Force ◽  
Tidal Breathing ◽  
First Line ◽  
Relaxation Effects ◽  
High Concentrations ◽  
Multiplicative Effects

Both isoproterenol and tidal fluctuations of muscle length inhibit active force development in activated airway smooth muscle. In this study, we show that length fluctuations in the range of amplitudes expected during quiet tidal breathing produce force inhibition that is equipotent with high concentrations of isoproterenol. Active force fell to 50% of its isometric value when the amplitude of the tidal stretch was 4% of muscle length. The relaxing effects of length fluctuations were insensitive to the specific contractile agonist, suggesting that the mechanism of action is largely independent of the particular signal transduction pathway and lies instead at the level of bridge dynamics. This idea is reinforced by the results of combining the relaxation effects of tidal fluctuations with those produced by isoproterenol at all but the highest concentrations studied (10−5 M). Such a combination produces multiplicative effects, indicating largely separate modes of action. These observations suggest that the tidal muscle stretches that are attendant to spontaneous breathing comprise the first line of defense against bronchospasm and that tidal muscle stretches may be the most important of all known bronchodilating agencies.

Latrunculin B increases force fluctuation-induced relengthening of ACh-contracted, isotonically shortened canine tracheal smooth muscle

2005 ◽  
Vol 98 (2) ◽  
pp. 489-497 ◽  
Author(s):  
M. L. Dowell ◽  
O. J. Lakser ◽  
W. T. Gerthoffer ◽  
J. J. Fredberg ◽  
G. L. Stelmack ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Actin Filament ◽  
Isometric Force ◽  
Muscle Length ◽  
Tracheal Smooth Muscle ◽  
Filament Length ◽  
Latrunculin B ◽  
Force Fluctuation ◽  
Reference Length

We hypothesized that differences in actin filament length could influence force fluctuation-induced relengthening (FFIR) of contracted airway smooth muscle and tested this hypothesis as follows. One-hundred micromolar ACh-stimulated canine tracheal smooth muscle (TSM) strips set at optimal reference length ( Lref) were allowed to shorten against 32% maximal isometric force (Fmax) steady preload, after which force oscillations of ±16% Fmax were superimposed. Strips relengthened during force oscillations. We measured hysteresivity and calculated FFIR as the difference between muscle length before and after 20-min imposed force oscillations. Strips were relaxed by ACh removal and treated for 1 h with 30 nM latrunculin B (sequesters G-actin and promotes depolymerization) or 500 nM jasplakinolide (stabilizes actin filaments and opposes depolymerization). A second isotonic contraction protocol was then performed; FFIR and hysteresivity were again measured. Latrunculin B increased FFIR by 92.2 ± 27.6% Lref and hysteresivity by 31.8 ± 13.5% vs. pretreatment values. In contrast, jasplakinolide had little influence on relengthening by itself; neither FFIR nor hysteresivity was significantly affected. However, when jasplakinolide-treated tissues were then incubated with latrunculin B in the continued presence of jasplakinolide for 1 more h and a third contraction protocol performed, latrunculin B no longer substantially enhanced TSM relengthening. In TSM treated with latrunculin B + jasplakinolide, FFIR increased by only 3.03 ± 5.2% Lref and hysteresivity by 4.14 ± 4.9% compared with its first (pre-jasplakinolide or latrunculin B) value. These results suggest that actin filament length, in part, determines the relengthening of contracted airway smooth muscle.

Pharmacological modulation of the mechanical response of airway smooth muscle to length oscillation

1997 ◽  
Vol 83 (3) ◽  
pp. 739-745 ◽  
Author(s):  
X. Shen ◽  
M. F. Wu ◽  
R. S. Tepper ◽  
S. J. Gunst
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Mechanical Response ◽  
Isometric Force ◽  
Shortening Velocity ◽  
Airway Reactivity ◽  
Pharmacological Modulation ◽  
Activation Mechanisms ◽  
Cross Bridges

Shen, X., M. F. Wu, R. S. Tepper, and S. J. Gunst. Pharmacological modulation of the mechanical response of airway smooth muscle to length oscillation. J. Appl. Physiol. 83(3): 739–745, 1997.—Stretch and retraction of the airways caused by changes in lung volume may play an important role in regulating airway reactivity. We studied the effects of different pharmacological stimuli on airway smooth muscle to determine whether the muscle behavior during length oscillation can be modulated pharmacologically and to evaluate the role of different activation mechanisms in determining its behavior during the oscillation. Active force decreased below the static isometric force during the shortening phase of length oscillation, resulting in an overall depression of force during the length oscillation cycle. This pattern of response was unaffected by the contractile stimulus or level of activation, suggesting that it was caused by a mechanism that is independent of the level of activation of cross bridges. The normalized area of the length-force hysteresis loop (hysteresivity) differed depending on the stimulus used for contraction. Effects of different stimuli on hysteresivity were not correlated with their effects on isotonic shortening velocity or isometric force, suggesting that the pharmacological modulation of the behavior of airway smooth muscle during length oscillation at these amplitudes cannot be accounted for by the effects on the cross-bridge cycling rate.

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