On the terminology for describing the length-force relationship and its changes in airway smooth muscle

2004 ◽  
Vol 97 (6) ◽  
pp. 2029-2034 ◽  
Author(s):  
Tony R. Bai ◽  
Jason H. T. Bates ◽  
Vito Brusasco ◽  
Blanca Camoretti-Mercado ◽  
Pasquale Chitano ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Underlying Mechanism ◽  
Force Generation ◽  
Dynamic Nature ◽  
Optimal Length ◽  
Maximal Force ◽  
Reference Length ◽  
Force Relationship

The observation that the length-force relationship in airway smooth muscle can be shifted along the length axis by accommodating the muscle at different lengths has stimulated great interest. In light of the recent understanding of the dynamic nature of length-force relationship, many of our concepts regarding smooth muscle mechanical properties, including the notion that the muscle possesses a unique optimal length that correlates to maximal force generation, are likely to be incorrect. To facilitate accurate and efficient communication among scientists interested in the function of airway smooth muscle, a revised and collectively accepted nomenclature describing the adaptive and dynamic nature of the length-force relationship will be invaluable. Setting aside the issue of underlying mechanism, the purpose of this article is to define terminology that will aid investigators in describing observed phenomena. In particular, we recommend that the term “optimal length” (or any other term implying a unique length that correlates with maximal force generation) for airway smooth muscle be avoided. Instead, the in situ length or an arbitrary but clearly defined reference length should be used. We propose the usage of “length adaptation” to describe the phenomenon whereby the length-force curve of a muscle shifts along the length axis due to accommodation of the muscle at different lengths. We also discuss frequently used terms that do not have commonly accepted definitions that should be used cautiously.

Force-length dependence of arterial lamellar, smooth muscle, and myofilament orientations

1987 ◽  
Vol 253 (5) ◽  
pp. H1141-H1147 ◽  
Author(s):  
J. G. Walmsley ◽  
R. A. Murphy
Keyword(s):  
Smooth Muscle ◽  
Force Generation ◽  
Angular Deviation ◽  
Optimal Length ◽  
Absolute Value ◽  
Average Decrease ◽  
Generating Capacity ◽  
Cellular Alignment ◽  
Elastic Laminae

Force generation by contractile elements of arterial tissue can be affected by alterations in their alignment with shortening. The orientation and morphometry of smooth muscle (SM) myofilaments, medial lamellae, and elastic laminae were examined as a function of length in intact swine carotid arteries or strips. Intimal-medial tissue strips were fixed during isometric contractions at lengths (L) defined with respect to the optimal length for force generation (Lo). The average orientation of SM cells in two perpendicular planes remained parallel to the long axis of the tissue at all lengths, but the absolute value of angular deviations increased with shortening. Tissue lengthening was associated with decreased folding of the elastic laminae. This decrease in waviness was quantified by a stretch index (SI). Ultrastructural observations indicated that the myofilament absolute angular deviation was greater than that for the cellular alignment. For arteries fixed in situ while constricted, SI was least in the periintimal laminae and increased in the peripheral laminae. The average decrease in force-generating capacity on shortening from Lo to 0.6 Lo attributed to increasing SM and myofilament angular deviations was calculated to be 7%.

Increase in passive stiffness at reduced airway smooth muscle length: potential impact on airway responsiveness

2010 ◽  
Vol 298 (3) ◽  
pp. L277-L287 ◽  
Author(s):  
Ynuk Bossé ◽  
Dennis Solomon ◽  
Leslie Y. M. Chin ◽  
Kevin Lian ◽  
Peter D. Paré ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Muscle Length ◽  
Passive Stiffness ◽  
Tidal Breathing ◽  
Reference Length ◽  
Length Reduction

The amplitude of strain in airway smooth muscle (ASM) produced by oscillatory perturbations such as tidal breathing or deep inspiration (DI) influences the force loss in the muscle and is therefore a key determinant of the bronchoprotective and bronchodilatory effects of these breathing maneuvers. The stiffness of unstimulated ASM (passive stiffness) directly influences the amplitude of strain. The nature of the passive stiffness is, however, not clear. In this study, we measured the passive stiffness of ovine ASM at different muscle lengths (relative to in situ length, which was used as a reference length, Lref) and states of adaptation to gain insights into the origin of this muscle property. The results showed that the passive stiffness was relatively independent of muscle length, possessing a constant plateau value over a length range from 0.62 to 1.25 Lref. Following a halving of ASM length, passive stiffness decreased substantially (by 71%) but redeveloped over time (∼30 min) at the shorter length to reach 65% of the stiffness value at Lref, provided that the muscle was stimulated to contract at least once over a ∼30-min period. The redevelopment and maintenance of passive stiffness were dependent on the presence of Ca2+ but unaffected by latrunculin B, an inhibitor of actin filament polymerization. The maintenance of passive stiffness was also not affected by blocking myosin cross-bridge cycling using a myosin light chain kinase inhibitor or by blocking the Rho-Rho kinase (RhoK) pathway using a RhoK inhibitor. Our results suggest that the passive stiffness of ASM is labile and capable of redevelopment following length reduction. Redevelopment and maintenance of passive stiffness following muscle shortening could contribute to airway hyperresponsiveness by attenuating the airway wall strain induced by tidal breathing and DI.

Airway smooth muscle contraction at birth: in vivo versus in vitro comparisons to the adult

1992 ◽  
Vol 70 (4) ◽  
pp. 590-596 ◽  
Author(s):  
John T. Fisher
Keyword(s):  
Smooth Muscle ◽  
Myosin Heavy Chain ◽  
Airway Smooth Muscle ◽  
Heavy Chain ◽  
Force Generation ◽  
Sectional Area ◽  
Cross Sectional ◽  
Maximal Force

It is clear from the literature that considerable postnatal development occurs in the contractile properties of skeletal and cardiac muscle. Nevertheless, few studies have focused on developmental changes in airway smooth muscle or on the functional capabilities of airway innervation in the newborn. Conclusions about force generation, based on measurements of pulmonary mechanics during stimulation of the vagus nerves, suggest that the newborn possesses a reduced capability to narrow airway diameter relative to the adult. This reduced in vivo response is accompanied by a reduction in maximal force generating capabilities when compared on the basis of force per unit tissue cross-sectional area (stress) in vitro. However, studies of porcine airways suggest that such a finding may simply reflect a reduction in the relative amount of contractile protein (myosin heavy chain) as seen in fetal or preterm smooth muscle. Thus, comparisons based on force normalized per cross-sectional area of myosin alter conclusions from one in which fetal tracheal smooth muscle generates less maximal force than the adult, to one in which the fetal trachea has greater contractile capabilities. Interestingly, comparisons of maximal isometric force in bronchial smooth muscle between different age groups remain unaffected when myosin heavy chain normalization is applied. Finally, there appears to be an age at which maximal force is significantly greater than at any other age, independent of the amount of smooth muscle (determined morphologically), smooth muscle myosin content, or myosin isoform. Whether this enhanced in vitro response is reflected in vivo, or is counteracted by other physiological mechanisms, remains to be seen.Key words: development, airway smooth muscle, lung resistance, force generation, normalization, myosin.

scholarly journals Methacholine causes reflex bronchoconstriction

1999 ◽  
Vol 86 (1) ◽  
pp. 294-297 ◽  
Author(s):  
Elizabeth M. Wagner ◽  
David B. Jacoby
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Bronchial Artery ◽  
Muscle Tension ◽  
Reflex Response ◽  
Resistance Change ◽  
Bilateral Vagotomy ◽  
Airways Resistance ◽  
Lower Airways

To determine whether methacholine causes vagally mediated reflex constriction of airway smooth muscle, we administered methacholine to sheep either via the bronchial artery or as an aerosol via tracheostomy into the lower airways. We then measured the contraction of an isolated, in situ segment of trachealis smooth muscle and determined the effect of vagotomy on the trachealis response. Administering methacholine to the subcarinal airways via the bronchial artery (0.5–10.0 μg/ml) caused dose-dependent bronchoconstriction and contraction of the tracheal segment. At the highest methacholine concentration delivered, trachealis smooth muscle tension increased an average of 186% over baseline. Aerosolized methacholine (5–7 breaths of 100 mg/ml) increased trachealis tension by 58% and airways resistance by 183%. As the bronchial circulation in the sheep does not supply the trachea, we postulated that the trachealis contraction was caused by a reflex response to methacholine in the lower airways. Bilateral vagotomy essentially eliminated the trachealis response and the airways resistance change after lower airways challenge (either via the bronchial artery or via aerosol) with methacholine. We conclude that 1) methacholine causes a substantial reflex contraction of airway smooth muscle and 2) the assumption may not be valid that a response to methacholine in humans or experimental animals represents solely the direct effect on smooth muscle.

Selected Contribution: Effect of chronic passive length change on airway smooth muscle length-tension relationship

2001 ◽  
Vol 90 (2) ◽  
pp. 734-740 ◽  
Author(s):  
Lu Wang ◽  
Peter D. Paré ◽  
Chun Y. Seow
Keyword(s):  
Smooth Muscle ◽  
Force Production ◽  
Muscle Length ◽  
Electrical Field Stimulation ◽  
Length Change ◽  
Electrical Field ◽  
Optimal Length ◽  
Active Length ◽  
Reference Length ◽  
Relationship Of

The ability of rabbit trachealis to undergo plastic adaptation to chronic shortening or lengthening was assessed by setting the muscle preparations at three lengths for 24 h in relaxed state: a reference length in which applied force was ∼1–2% of maximal active force (Po) and lengths considerably shorter and longer than the reference. Passive and active length-tension ( L-T) curves for the preparations were then obtained by electrical field stimulation at progressively increasing muscle length. Classically shaped L-T curves were obtained with a distinct optimal length ( L o) at which Podeveloped; however, both the active and passive L-T curves were shifted, whereas Po remained unchanged. L o was 72% and 148% that of the reference preparations for the passively shortened and lengthened muscles, respectively. The results suggest that chronic narrowing of the airways could induce a shift in the L-T relationship of smooth muscle, resulting in a maintained potential for maximal force production.

Selected Contribution: Mechanical strain increases force production and calcium sensitivity in cultured airway smooth muscle cells

2000 ◽  
Vol 89 (5) ◽  
pp. 2092-2098 ◽  
Author(s):  
Paul G. Smith ◽  
Chaity Roy ◽  
Steven Fisher ◽  
Qi-Quan Huang ◽  
Frank Brozovich
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Force Production ◽  
Muscle Cells ◽  
Calcium Sensitivity ◽  
Airway Smooth Muscle Cells ◽  
Maximal Force

Cultured airway smooth muscle cells subjected to cyclic deformational strain have increased cell content of myosin light chain kinase (MLCK) and myosin and increased formation of actin filaments. To determine how these changes may increase cell contractility, we measured isometric force production with changes in cytosolic calcium in individual permeabilized cells. The pCa for 50% maximal force production was 6.6 ± 0.4 in the strain cells compared with 5.9 ± 0.3 in control cells, signifying increased calcium sensitivity in strain cells. Maximal force production was also greater in strain cells (8.6 ± 2.9 vs. 5.7 ± 3.1 μN). The increased maximal force production in strain cells persisted after irreversible thiophosphorylation of myosin light chain, signifying that increased force could not be explained by differences in myosin light chain phosphorylation. Cells strained for brief periods sufficient to increase cytoskeletal organization but insufficient to increase contractile protein content also produced more force, suggesting that strain-induced cytoskeletal reorganization also increases force production.

Cyclooxygenase inhibitors increase canine tracheal muscle response to parasympathetic stimuli in situ

1990 ◽  
Vol 68 (6) ◽  
pp. 2597-2603 ◽  
Author(s):  
R. A. Bethel ◽  
C. L. McClure
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Cyclooxygenase Inhibitors ◽  
Muscarinic Agonist ◽  
Vagus Nerves ◽  
Lipoxygenase Inhibitor ◽  
Mediators Of Inflammation ◽  
Parasympathetic Control

To determine whether cyclooxygenase inhibitors alter parasympathetic control of airway smooth muscle in situ, we pretreated anesthetized dogs with intravenous indomethacin, meclofenamate, or normal saline and measured the isometric contraction of tracheal muscle in response to electrical stimulation of the vagus nerves. Indomethacin and meclofenamate increase the response of airway smooth muscle to parasympathetic stimulation. In subsequent experiments to determine the site of action of cyclooxygenase inhibitors, we found that indomethacin does not alter the response of tracheal muscle to intra-arterial acetylcholine (a muscarinic agonist) but does augment the response to intra-arterial dimethylpiperaziniumiodide (a nicotinic agonist). Moreover, the response to parasympathetic stimulation after pretreatment with a combination of indomethacin and BW755C (a combined cyclooxygenase-lipoxygenase inhibitor) does not differ significantly from the response after indomethacin or meclofenamate alone. We conclude that cyclooxygenase inhibitors increase the sensitivity of the contractile response of tracheal smooth muscle to parasympathetic stimulation, that they exert their effect on the postganglionic parasympathetic neuron, and that their effect is prejunctional. The effect appears secondary to a decrease in cyclooxygenase products rather than to an increase in lipoxygenase products. These findings suggest that endogenous cyclooxygenase products may modulate parasympathetic control of airway smooth muscle in vivo. They may relate to the mechanisms that underlie airway hyperresponsiveness, by which mediators of inflammation modulate airway responsiveness and by which nonsteroidal anti-inflammatory drugs induce severe bronchoconstrictor responses in some persons who have asthma.

Mechanical strain modulates maximal phosphatidylinositol turnover in airway smooth muscle

1999 ◽  
Vol 277 (5) ◽  
pp. L968-L974 ◽  
Author(s):  
Steven S. An ◽  
Chi-Ming Hai
Keyword(s):  
Smooth Muscle ◽  
G Proteins ◽  
Airway Smooth Muscle ◽  
Mechanical Strain ◽  
Muscle Length ◽  
Heterotrimeric G Proteins ◽  
Maximal Level ◽  
Optimal Length ◽  
Pi Turnover ◽  
Length Dependence

Mechanical strain regulates the maximal level of myosin light chain phosphorylation mediated by muscarinic activation in airway smooth muscle. Accordingly, we tested the hypothesis that mechanical strain regulates maximal phosphatidylinositol (PI) turnover ( V max) coupled to muscarinic receptors in bovine tracheal smooth muscle. We found that PI turnover was not significantly length dependent in unstimulated tissues. However, carbachol-induced PI turnover was linearly dependent on muscle length at both 1 and 100 μM. The observed linear length dependence of PI turnover at maximal carbachol concentration (100 μM) suggests that mechanical strain regulates V max. When carbachol concentration-PI turnover relationships were measured at optimal length and at 20% optimal length, the results could be explained by changes in V max alone. To determine whether the length-dependent step is upstream from heterotrimeric G proteins, we investigated the length dependence of fluoroaluminate-induced PI turnover. The results indicate that fluoroaluminate-induced PI turnover remained significantly length dependent at maximal concentration. These findings together suggest that regulating functional units of G proteins and/or phospholipase C enzymes may be the primary mechanism of mechanosensitive modulation in airway smooth muscle.

scholarly journals Emergence of airway smooth muscle functions related to structural malleability

2011 ◽  
Vol 110 (4) ◽  
pp. 1130-1135 ◽  
Author(s):  
Chun Y. Seow ◽  
Jeffrey J. Fredberg
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Molecular Interactions ◽  
Indirect Evidence ◽  
Emergent Properties ◽  
Structural Elements ◽  
Molecular Events ◽  
Cell Dimensions ◽  
Active Interaction ◽  
Force Relationship

The function of a complex system such as a smooth muscle cell is the result of the active interaction among molecules and molecular aggregates. Emergent macroscopic manifestations of these molecular interactions, such as the length-force relationship and its associated length adaptation, are well documented, but the molecular constituents and organization that give rise to these emergent muscle behaviors remain largely unknown. In this minireview, we describe emergent properties of airway smooth muscle that seem to have originated from inherent fragility of the cellular structures, which has been increasingly recognized as a unique and important smooth muscle attribute. We also describe molecular interactions (based on direct and indirect evidence) that may confer malleability on fragile structural elements that in turn may allow the muscle to adapt to large and frequent changes in cell dimensions. Understanding how smooth muscle works may hinge on how well we can relate molecular events to its emergent macroscopic functions.

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