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Department of Anatomy and Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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The ability of arterial smooth muscle to generate tension is influenced by muscle length. An unsettled question is whether the length-tension relationship is a simple reflection of the contractile filament overlap, as it is in skeletal muscle. There are several factors that could potentially affect tension generation in arterial smooth muscle; these include stretch-induced myogenic response and length-oscillation-induced disruption of the contractile filament organization. In this study, in which rabbit carotid arterial preparations were used, we found that different length-tension curves could be obtained at different times after a length change. In addition, length oscillation at a frequency of normal pulse rate and with small to moderate oscillation amplitude was found to potentiate tension generation but reduced tension at large amplitudes. The observed response could be attributed to adaptation of the muscle to length change over time and to myogenic potentiation associated with stretching of the muscle.
carotid artery; length oscillation; tension recovery; plasticity
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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TENSION PRODUCTION IN MUSCLE tissue is affected by muscle length. In striated muscle, active tension is primarily a function of the extent of overlap of the contractile filaments (8); therefore, the length-tension relationship found in striated muscle provides a strong support for the sliding-filament and cross-bridge model of muscle contraction (12-14). The resemblance of smooth muscle to striated muscle in terms of length-tension behavior (19) seems to suggest that the same contractile mechanism is operative in smooth muscle, although a sarcomere-like contractile unit has never been clearly delineated in smooth muscle. On closer examination, length-tension curves of smooth muscle differ from that of striated muscle in at least four aspects. 1) Length-tension curves from various types of smooth muscle possess a rather broad plateau of maximum tension (9, 11, 18, 24), suggesting that the structure of the force-generating apparatus in smooth muscle may be different from that of striated muscle. 2) Phosphorylation of the regulatory myosin light chain (MLC) is length dependent (16, 22, 25, 28, 30, 33); therefore, tension generation in smooth muscle is not strictly a function of the contractile filament overlap. 3) Adaptation of smooth muscle to length change through reorganization of intracellular structures to maximize force production (10, 20) tends to alter the shape of the length-tension curve over time. 4) The stretch-induced myogenic response in some smooth muscles, including arterial smooth muscle (4), has a direct influence on the length-tension relationship. Therefore, the close relationship between contractile filament overlap and the shape of the length-tension curve seen in skeletal muscle may not exist in smooth muscle. An accurate description of the length-tension relationship in smooth muscle contraction is important not only for theoretical considerations. It also has important practical implications because smooth muscle functions in hollow organs whose physiological dimensions are intimately related to the length-tension relationship of the muscle, whether this relationship is entirely governed by the contractile filament overlap or otherwise. Previous studies on the length-tension characteristics of smooth muscle have regarded the relationship as static (11, 18, 24) on the basis of the assumption that the subcellular structure from which the length-tension behavior arises is permanent, as in striated muscle. Some recent observations have revealed substantial plasticity in the structure and function of some smooth muscles (6, 7, 10, 20, 29, 32) with the ability to accommodate large length changes without compromising the ability to generate tension. A static length-tension curve therefore is not adequate to describe the dynamic process of adaptation. In this study, the length-tension behavior of arterial smooth muscle is characterized as a relationship that changes with time, paralleling the process of adaptation and other mechanical responses following length perturbation.
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MATERIALS AND METHODS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Adult New Zealand White rabbits weighing 2-3 kg were used for the experiments. The animals were euthanized in a CO2 chamber. A segment of the common carotid artery was quickly removed and kept in ice-cold physiological saline solution until use. All experiments were carried out at 37°C in physiological saline at pH 7.4 aerated with a 5% CO2-95% O2 mixture and containing (in mM) 118 NaCl, 5 KCl, 1.2 NaH2PO4, 22.5 NaHCO3, 2 MgSO4, and 2 CaCl2 and 2 g/l dextrose.
Muscle Preparation
Loose connective tissue associated with the adventitia was dissected away, and the endothelial layer was removed by gently rubbing the luminal side of the artery with a pair of forceps. A ring of the artery, ~1 mm wide, was then cut from the segment. Because only loose connective tissues were removed, the artery ring retained its in vivo mechanical integrity. This is important for correlating results from the in vitro experiments to the in vivo behavior of the artery. The artery ring was mounted on the apparatus horizontally, stretched between two L-shaped stainless steel wires that were extensions of a force transducer and a servomotor. Each muscle preparation was allowed to adapt to the experimental condition for ~1 h while being stimulated to produce tetani of 16-s duration at 5-min intervals. During this adaptation period, the circumferential length associated with maximal tension production was identified and used as a reference length (Lref). The circumferential length was calculated as twice the distance between the centers of the stainless steel wires plus the portions (semicircles) supported by the wires. The diameter of the stainless steel wire was 0.3 mm, and the thickness of the ring segment was ~0.1 mm at Lref. It was assumed that the tissue volume of the ring segment remained constant at different circumferential lengths; therefore, the ring thickness became thinner at longer lengths. This variation in thickness was taken into consideration when calculating the circumferential length of the ring.Apparatus
A photoelectric type of force transducer was used for force measurement. The resonant frequency of the transducer was ~5 kHz. A loudspeaker-type linear motor was used to apply sinusoidal oscillations to the muscle preparation. A function generator produced the sinusoidal signal and also controlled the amplitude and frequency of the signal. The highest frequency of oscillation that the motor could follow was ~1 kHz. A line-frequency (60 Hz) stimulator was used to provide supramaximal electrical field stimulation through two parallel platinum electrodes. Force and length signals were digitized with a computer equipped with an analog-to-digital converter (National Instrument, model PCI6023E) with a maximum sampling rate of 250 kHz. The computer also controlled onsets of stimulation and oscillation during the experiments.Protocols
Length-tension curve. During the equilibration period, the length (Lref) of the muscle that was associated with maximal tension (To) generation was determined. Because the rabbits were all very similar in size, the size of the carotid arteries was virtually identical. This made determination of Lref relatively easy because it varied very little from one preparation to the next. Once the preparation was in a steady state in terms of force generation, isometric tension at the plateau of contraction was measured at different muscle lengths. The optimal length (Lref) was used as a reference; four other lengths were then calculated according to this reference length: 0.67, 0.83, 1.17, and 1.33 Lref. This range covered exactly a twofold length variation. The muscle length was changed from Lref to one of the above four lengths in random order. Once it was set to a new length, a 2-min period was allowed for the passive viscoelastic response of the muscle to settle, an electrical stimulus was then applied to elicit an isometric contraction, and the maximum isometric tension was measured. The muscle was then allowed to adapt at that length for ~30 min while it was stimulated isometrically once every 5 min. After the adaptation period, the muscle length was returned to Lref, followed by another 30-min adaptation period before the muscle length was changed again. Isometric tension measurement at any of the four test lengths was therefore "bracketed" by measurements of isometric tension at Lref before and after the test measurement. The test result was normalized by the average of the reference tensions obtained before and after the length change. This ensured that the tension decline due to deterioration of muscle tissue did not affect the results. The decline of reference tension during the entire course of an experiment for any preparations used did not exceed 10% of initial maximum isometric reference tension (To).
Wall tension of the vessel was obtained by dividing isometric tension measured in the ring preparation by two. The wall tension was initially expressed in units of force per unit axial length of the vessel (mN/mm); it was later normalized by the optimal tension of the preparation (To). The segment length was also the width of the artery ring. The thickness of the vessel wall was assumed to be the same for all preparations because of the similarity in size in all the carotid arteries used.Oscillation-induced tension change. Length oscillations of various amplitudes were applied to a relaxed (or unstimulated) muscle preparation at a frequency of 250 cycles/min (4.17 Hz). The frequency was chosen to mimic heart rate in rabbits (3). The oscillation was symmetrical about the mean length of the muscle. Duration of the oscillation was 200 s. Immediately after the period of oscillation, the muscle was stimulated isometrically and the tension was assessed. The muscle was then allowed to "recover" for ~30 min during which it was stimulated once every 5 min without any further length perturbation. After the muscle had recovered, another period of length oscillation with a different amplitude was then applied, followed by isometric tension assessment and recovery for 30 min. The process repeated itself 10 times with 10 different oscillation amplitudes.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Adaptation of Muscle at Different Lengths
When muscle length was changed from Lref to other lengths (0.67, 0.83, 1.17, and 1.33 Lref), isometric tension decreased substantially (see those obtained 2 min after length change in Fig. 1A). Isometric tension recovered significantly (see those obtained 27 min after length change in Fig. 1A) after an adaptation period during which the muscle was stimulated at the same length once every 5 min. Two-way ANOVA showed that the means from the two groups of data (partially and fully adapted tension measurements) were significantly different from one another (P < 0.01).
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The range of length over which active tension was assessed was associated with substantial passive tension. Maximal tension occurs at a length at which passive tension was slightly higher than the active tension. Figure 1B shows passive (or unstimulated) length-tension curves obtained at the same time from the same preparations in which the active length-tension curves in Fig. 1A were obtained. The passive curves were well described by monoexponential functions (fitted curves, Fig. 1B). The characteristics of recovery of passive tension after length change reflected viscoelastic properties of the preparation; the partially adapted curve (represented by open circles) appeared to be stiffer compared with the fully adapted curve (represented by solid circles), judging from the average slopes of the passive length-tension curves (Fig. 1B). The two curves crossed each other at Lref; this was because the fully adapted passive tension at Lref was used as a reference for passive tensions measured at other lengths and different times. The same protocol of normalizing tension by fully adapted tension at Lref was also used for obtaining the active length-tension curves shown in Fig. 1A.
Time Course of Tension Recovery After Length Change
The time courses of tension recovery at different lengths were different. At lengths shorter than Lref, tension recovery as a function of time could be described by a single exponential function (Fig. 2A). To facilitate comparison of the recovery process at different lengths, tension obtained during recovery was normalized by tension obtained at the end of the recovery (or adaptation) period (Tfinal, shown as solid circles in Fig. 1A). The parameters for the exponential functions used to fit the data in Fig. 2A are listed in Table 1. The rate constants in both of the recovery processes (at lengths 0.67 and 0.83 Lref) are not significantly different from each other. At lengths longer than Lref, tension recovery as a function of time was more complicated and could not be fitted with a single exponential function (Fig. 2B). The two recoveries at the two lengths (1.17 and 1.33 Lref) followed a similar time course. It should be pointed out, however, that the recoveries shown in Fig. 2B were normalized to their respective final tension levels reached at the end of the adaptation period (Tfinal); the first and last points of the recoveries were quite different in absolute terms.
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Circumferential Length Change Due to Pulsatile Blood Pressure
Figure 3 shows tension response to sinusoidal length oscillation applied to an unstimulated arterial ring preparation. The preparation was stretched to give a mean tension that corresponded approximately to the mean blood pressure of rabbits (3). Pressure values were calculated with the use of the Laplace equation (for thin-walled cylindrical vessels), T = P × R, where T is the vessel-wall tension (per unit length of the cylindrical vessel, or width of the artery ring segment), P is pressure inside the vessel, and R is the radius of the vessel or artery ring, which is assumed to have a circular profile under distending pressure. Values of R were calculated from the circumferential length, R = (circumferential length)/2
. The tension vs. length plot (Fig. 3C) shows
hysteresis in the preparation, caused by a small viscous component that
also resulted in a phase shift of about 5° (or 0.0873 rad) between the tension response and the length oscillation. The phase shift was
estimated by shifting horizontally the trace of tension oscillation (Fig. 3B) with respect to the trace of length oscillation
(Fig. 3A) until the hysteresis disappeared in the
length-tension plot (Fig. 3C), that is, until the "gap"
in the loop disappeared. Due to the presence of viscosity, the apparent
stiffness (average slope in Fig. 3C) of the blood vessel
wall estimated by length oscillation at a physiological frequency of
4.17 Hz (250 beats/min) was higher than that obtained from the average
slope at the same tension range in Fig. 1B.
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Wall tension (Fig. 3C) was converted to pressure according
to the Laplace equation. The value for mean blood pressure (12 kPa) was
taken from measurements made in anesthetized rabbits (3).
The diastolic and systolic pressures were 10.7 and 16.0 kPa,
respectively. By varying the amplitude of the length oscillation, a
tension variation corresponding to a pressure variation of
10.7-16.0 kPa was obtained, and the amplitude of the driving
length oscillation was taken as the length variation associated with
the pulsatile blood pressure. Averaged results from six preparations (3 rabbits) are summarized as follows: passive vessel wall stiffness,
71.3 ± 3.4 mN · mm
1 · Lref1;
estimated length variation corresponding to blood pressure variation, 11.6 ± 0.57% Lref; phase shift between
force response and length oscillation, 0.084 ± 0.008 rad.
Oscillation-Induced Tension Change in the Subsequent Contractions
Length oscillation such as that shown in Fig. 3 was found to affect the subsequent isometric tension generation. Figure 4 shows isometric tension measured in a brief tetanus elicited immediately after termination of passive length oscillation. The period of oscillation was 200 s, long enough for the passive tension response to reach a steady state. The length oscillation was centered on Lref, and the amplitudes (peak to peak) used were from 2 to 56% Lref. The amount of stretch beyond Lref was therefore one-half of the peak-to-peak amplitudes, that is, 1 to 28% Lref. Small-amplitude oscillation caused potentiation in the subsequent contraction, whereas large-amplitude oscillation caused reduction in tension generation. The "crossover" point was somewhere between 32 and 40% Lref of oscillation amplitudes.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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There are two new findings in this study. The first is that the length-tension relationship in vascular smooth muscle is time dependent; this suggests that the ultrastructure determining the length-tension relationship in this muscle may not be static but likely plastic, and it allows the muscle to adapt to large length changes without greatly reducing the ability of the muscle to generate force. Plasticity is a relatively well-characterized property in airway smooth muscle (10, 20, 27), but it has never been described for vascular smooth muscle. The second finding is the biphasic behavior of postoscillation tension generation as a function of oscillation amplitude. At small to moderate amplitudes, length oscillation potentiates tension generation, whereas, at large amplitudes, it reduces tension generation. The subcellular and molecular mechanisms for these observations are not clearly understood; therefore, functional characterization of these phenomena provided by the present study will be useful in guiding experiments seeking to elucidate the underlying mechanisms.
A recent description of plastic adaptation in airway smooth muscle to length change (20) suggests that structural reorganization at the contractile filament level may accompany changes in cell length. The subcellular structures that determine the length-tension relationship in smooth muscle therefore seem to be labile and are susceptible to disruption by alterations in cell length. This implies that the protocol used to determine the length-tension relationship in smooth muscle, which involves alteration of muscle length, will itself interfere with the outcome of the measurement. As revealed in Fig. 1, different length-tension curves can be obtained under different conditions. If a steady-state length-tension relationship is sought, adaptation of the muscle at each of the lengths has to be allowed. In vivo function of smooth muscle, however, is not always best characterized by steady-state relationships. Airway and arterial smooth muscles, for example, are always subjected to periodic mechanical perturbations, due to tidal breathing and pulsatile blood pressure. A complete understanding of smooth muscle function therefore involves characterization of both steady-state and non-steady-state properties.
Active Length-Tension Curves
Distinctly different length vs. active tension curves can be obtained at different times after length change, as illustrated in Fig. 1A. This is because isometric force recovers from an initial drop after a length change. The extent of recovery seems to be different for different types of smooth muscle. In airway smooth muscle, full recovery of force is achieved as long as the length change is within a threefold length range (20), revealing the great ability of the muscle to accommodate alterations in cell geometry. Compared with airway smooth muscle, arterial smooth muscle has a limited capability to adapt. Nevertheless, significant force recovery can be achieved after a length change, if adequate time is allowed for the accommodation to occur. The maximum tension variation over the twofold length range (centered around Lref) found in rabbit carotid smooth muscle (Fig. 1A) is 0.145 To in the adapted state. The tension variation within a comparable length range in frog semitendinosus muscle is ~0.7 To (8). In canine tracheal smooth muscle, tension variation within the twofold length range is zero (20).Passive Length-Tension Curves
In vivo function of large arteries depends critically on the passive mechanical properties of the vessels. The elastic property of the vessel is important in absorbing and restoring energy associated with the pulsatile blood pressure and moderating systolic and diastolic pressure differences and thus reducing potential damage to the blood vessel itself. The passive property of the vessel is not purely elastic, as suggested by the results shown in Fig. 1B. Like the active length-tension relationship (Fig. 1A), the passive relationship is also time dependent. The curves obtained 2 and 27 min after length change (Fig. 1B) are different (two-way ANOVA, P < 0.05). The difference can be attributed to the viscoelastic property of the tissue because the passive tension recovery exhibits a typical time course of stress relaxation after a step length change. In a swine arterial preparation, Rembold (21) described a very similar behavior of the tissue at resting state. The stress relaxation in the unstimulated arterial preparation appeared to be independent of cross-bridge interaction in this preparation (21). After repeated activation, remodeling of the tension-bearing cytoskeletal filament network may occur, which would in turn alter the passive length-tension relationship (31).Recovery of Active Tension after Length Change
Tension recovery after passive shortening. Immediately after passively shortening the muscle length, the subsequently elicited active tension is reduced substantially compared with the steady-state tension before the length change. The muscle tension then recovers toward the level before the length release. In arterial smooth muscle, this recovery is incomplete. The partial recovery, however, is significant and represents a substantial improvement in the tension-generating ability of the muscle. The time course of the recovery (revealed by eliciting isometric contractions at 5-min intervals) is well described by a single-term exponential equation (Fig. 2A and Table 1). A larger length change is associated with a larger initial decrease in tension; the rate of recovery, however, is not affected by the size of the step length release. The rate constants for the two recoveries (at 0.67 and 0.83 Lref) are not statistically different (Table 1). The underlying mechanism for the monoexponential tension recovery is not clear, but it appears that the same mechanism governs recoveries from different sizes of length release. In tracheal smooth muscle, a similar time course of tension recovery is observed after a length change, which can be a stretch or a release (20) or an oscillation (27), and the same exponential function can be used to describe the tension recoveries. In arterial smooth muscle, tension recovery from a step length stretch follows a different time course, as described in detail next.
Tension recovery after a stretch. Stretching of the muscle beyond its optimal length results in a decrease in isometric tension, as shown in Fig. 1. After this initial decrease, isometric tension recovers significantly over a period of time, as it does after a step length release. Unlike the recovery after a release, tension recovery after a stretch cannot be described by a single exponential process; it follows a more complex time course, possibly consisting of two or more independent processes initiated only by stretch of the muscle. The apparent rate of recovery is increased after a stretch (Fig. 2B). Because it is not possible to measure isometric tension at smaller intervals (<5 min) due to the minimal time (5 min) required for the muscle in this preparation to reach a fully relaxed and metabolically rejuvenated state after an isometric contraction, details of the time course of tension recovery between 0 and 5 min cannot be obtained. Stretching the muscle could simply increase the rate of recovery, or it could evoke other responses from the muscle.
Stretching of arterial smooth muscle, especially that of small arteries and arterioles, is known to induce muscle contraction, a phenomenon known as the myogenic response (4). This may be responsible for the deviation from monoexponential recovery seen in the absence of myogenic response, that is, after a step release (Fig. 2A). In some muscles (for example, airway smooth muscle) that do not possess stretch-induced myogenic response, the same monoexponential recovery is observed after either a release or a stretch (20).Myogenic Potentiation
Stretch-induced arterial or arteriolar constriction has been well documented and attributed to myogenic mechanisms, independent of neural, metabolic, and hormonal influences (2, 4, 5). Stretching of carotid arterial smooth muscle does not induce spontaneous contraction; therefore, it is said that the muscle does not possess myogenic response. This, however, does not mean that the stretch has no effect on the muscle. Small to moderate length perturbations potentiate subsequent contractions in the muscle elicited by electric field stimulation, as found in this study (Fig. 4). Myogenic potentiation differs, therefore, from a typical myogenic response in the lack of spontaneous contraction, although the stretch obviously enhances the active state in the muscle. In swine carotid media, Rembold and Murphy (22) found that stretches from 0.7 to 1.0 Lo and from 1.0 to 1.2 Lo significantly increased myoplasmic Ca2+ concentration without increasing MLC phosphorylation and the associated force generation. Bárány et al. (1), on the other hand, found a transient increase in MLC phosphorylation in stretched arterial smooth muscle and a spontaneous contraction on release from stretch (myogenic response). The present finding of a potentiated state after length oscillation at certain amplitudes could be explained by the results of Rembold and Murphy; that is, elevated myoplasmic Ca2+ concentration could be responsible for the potentiation. Other explanations cannot be excluded. Shue and Brozovich (23) suggested that a certain population of attached cross bridges in the relaxed state could enhance force generation in a subsequent contraction. The basic mechanism underlying the phenomena of myogenic response and myogenic potentiation could be the same, although more studies are required to resolve this issue (4). Perhaps it is because of the lack of spontaneous contraction in most large arteries in response to stretch that studies of myogenic response are mainly focused on small arteries or arterioles that constrict when stretched or pressurized (in cannulated vessels) without further stimulation. The importance of myogenic response in autoregulation of flow resistance in small blood vessels is obvious; the physiological role of myogenic potentiation in large arteries is not apparent. This muscle property, however, has a direct effect on the shape of the length-tension curve.Passive Oscillation-Induced Tension Change in Subsequent Contractions
Effect of oscillation amplitude. The in vivo pulsatile circumferential length variation in carotid artery is a substantial fraction of Lref. The magnitude of stretch applied to the encircling smooth muscle layer in the blood vessel due to pressure fluctuation is enough to induce myogenic potentiation. As shown in Fig. 4, myogenic potentiation can be elicited by a length oscillation with an amplitude as small as 2% Lref or a 1% Lref stretch. At 11.6% Lref, the amplitude corresponding to the in vivo length fluctuation amplitude due to pulsatile blood pressure, myogenic potentiation reaches a peak (Fig. 4). It is not clear whether this is a coincidence or whether there is any physiological significance to this phenomenon.
As the applied oscillation amplitude increases beyond the physiological range, myogenic potentiation diminishes; at amplitudes of ~34% Lref, oscillation-induced myogenic potentiation disappears. A further increase in the amplitude of oscillation results in a decrease in tension generation (Fig. 4). This biphasic response suggests that there could be two competing processes responsible for the oscillation-induced changes in the ability of smooth muscle to generate tension. In tracheal smooth muscle, a preparation that does not exhibit myogenic response, the biphasic response to length oscillation is absent (27). Instead, tension decreases linearly with amplitude of oscillation, similar to the solid straight line shown in Fig. 4. Length perturbation applied to a relaxed smooth muscle is potentially capable of disrupting contractile filament organization and causing a tension decrease in the subsequent contractions. This is possibly a contributing factor to the initial decrease in tension after a length change. In tracheal smooth muscle, a large decrease in tension is observed immediately after a length change, whether it is a release or a stretch (20); the tension then recovers completely over a period of ~30 min, as the muscle becomes adapted to the new length, possibly through reorganization of the contractile filaments to optimize their overlap. Oscillation applied to tracheal smooth muscle has the same effect as a step length change; the subsequent tension recovery after oscillation follows a similar time course as that after a step length change (27). Length oscillation, therefore, appears to have the same disrupting effect on the subsequent tension generation as a step length change. The degree of disruption is proportional to the amplitude of oscillation. In arterial smooth muscle, the presence of myogenic potentiation complicates the relationship between oscillation amplitude and the subsequent tension generation. If stretching of the muscle is avoided, as in a step length release (Fig. 2A), the recovery of tension is monoexponential, suggesting that only the disrupting effect is involved in a step length release. Stretching the muscle, on the other hand, involves both disrupting and potentiating effects. If we assume that the potentiating and disrupting effects are additive, the biphasic response of tension to oscillation amplitude can be dissected into two monophasic components: a linear decline of tension due to disruption of the contractile filaments as oscillation amplitude increases (solid line in Fig. 4) and a monoexponential increase, which reaches a maximum due to myogenic potentiation (dotted line in Fig. 4). Summing up the two processes produces a good fit to the data (dashed line in Fig. 4). At small amplitudes of oscillation, potentiation of tension generation dominates the response; at large amplitudes, disruption of the contractile machinery results in tension decrease. The assumption that the two processes are additive could be an oversimplification; there may be a synergistic relationship between them. However, in the absence of further evidence to suggest otherwise, the simplest model is presented here.Transient nature of the tension potentiation/depression after termination of length oscillation. The change in tension after length oscillation observed in Fig. 4 returns to baseline in ~5 min. Because it is not possible to assess isometric tension in intervals less than 5 min without causing "fatigue" in the muscle preparation, the details of the time course of recovery cannot be delineated with reliable accuracy. It is important to note that the disrupting and potentiating effects of length oscillation do not result in an irreversible change in the ability of the muscle to generate tension.
Comparison to other smooth muscles. Airway smooth muscle, compared with arterial smooth muscle, seems to represent a more basic form of smooth muscle in terms of its function. Smooth muscle cells lining the walls of hollow organs are often required to function over an enormous length range. For example, smooth muscle cells in a urinary bladder are required to undergo severalfolds of length change to fulfill their physiological function (26). To accommodate the drastic alteration in cell geometry and retain proper contractile filament overlap, smooth muscle may have evolved a mechanism that allows the cell to undergo plastic rearrangement of its contractile apparatus (10, 20). A change in the resting cell length may be the signal that initiates the plastic rearrangement, which starts by disassembling the existing apparatus before reassembling it again to suit the new cell dimension. This may be the reason for the initial decrease in isometric tension after a length perturbation and the subsequent monoexponential tension recovery. It is likely that arterial smooth muscle retains this basic property of plasticity, as suggested by the results of this study. Physiological function also requires arteries, especially small arteries and arterioles, to possess myogenic response, another length-perturbation-induced muscle reaction. The theoretical description of data presented in Fig. 4 assumes that both plastic adaptation and myogenic potentiation are induced by length perturbation.
Physiological Implications of a Dynamic Length-Tension Relationship
With the variation in blood pressure, smooth muscle lining the arterial wall is constantly subjected to length change. Results from this study have demonstrated that arterial smooth muscle behaves very differently in a dynamic environment, compared with that in a static state. It is clear, therefore, that our understanding of the in vivo function of artery critically depends on our understanding of the dynamic properties of arterial smooth muscle. Another important cell type in an intact artery, which could potentially affect the mechanical properties of the blood vessel, is endothelium. Vascular wall stretch or distension could induce the release of an endothelium-derived vasoconstrictor substance or decrease the endogenous release of endothelium-derived relaxing factor (15). However, a majority of the studies indicates that endothelial cells are not required for a normal myogenic response (17). In light of the time dependence of the length-tension relationship in smooth muscle, our prediction of isometric tension based on a length-tension curve has to include a time dimension. The finding that small to moderate amplitude of length oscillation potentiates isometric tension implies that arterial smooth muscle in vivo is always in a potentiated state.| |
ACKNOWLEDGEMENTS |
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Special thanks to Dr. Richard W. Mitchell for helpful discussion and comments on the manuscript.
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FOOTNOTES |
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This study was supported by a grant-in-aid from the Heart and Stroke Foundation of British Columbia and Yukon and an operating grant from the Medical Research Council of Canada (MT-13271).
Original submission in response to a special call for papers on "Cellular Responses to Mechanical Stress."
Address for reprint requests and other correspondence: C. Y. Seow, Dept. of Anatomy and Dept. of Pharmacology and Therapeutics, Univ. of British Columbia, 2176 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3 (E-mail: cseow{at}interchange.ubc.ca).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 30 May 2000; accepted in final form 18 July 2000.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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) and 27 min after length change
(
). Reference length (Lref) = 2.25 ± 0.04 (SE) mm; maximal isometric tension
(To) = 5.84 ± 0.36 (SE) mN/mm. Values are means ± SE; n = 11 experiments.
