Correlation between active and passive isometric force and intramuscular pressure in the isolated rabbit tibialis anterior muscle

The purpose of this study was to quantify the relationship between intramuscular pressure (IMP) and muscle force during isometric muscle contraction of the rabbit tibialis anterior (TA) absent the effect of either bone or fascia. To quantify this relationship, length-tension experiments were performed on the isolated TA of the New Zealand White rabbit (mass=2.5+/-0.5kg, n=12). The knee was fixed in a custom jig, the distal tendon of the TA was attached to a servomotor, and a 360 microm fiber optic pressure transducer was inserted into the TA. The peroneal nerve was stimulated to define optimal length (L(0)). The length-tension curve was created using 40Hz isometric contractions with 2-min rest intervals between each contraction. Measurements began at L(0)-50%L(f) and progressed to L(0)+50%L(f), changing the length-tension in 5% L(f) increments after each contraction. Qualitatively, the length-tension curve for isometric contractions was mimicked by the length-pressure curve for both active and passive conditions. Linear regression was performed individually for each animal for the ascending and descending limb of the length-tension curve and for active and passive conditions. Pressure-force coefficients of determination ranged from 0.138-0.963 for the active ascending limb and 0.343-0.947 for the active descending limb. Passive pressure coefficients of determination ranged from 0.045-0.842 for the ascending limb and 0.672-0.982 for the descending limb. These data indicate that IMP measurement provide a fairly accurate index of relative muscle force, especially at muscle lengths longer than optimal.     

The dynamical stability of isometrically contracting muscle and its relation to transient force response

The length-tension relation for tetanically contracting muscle indicates that for lengths longer than the resting length, the muscle should be dynamically unstable; i.e. some sarcomeres should lengthen and others shorten. This behavior is not observed experimentally. The theoretical behavior of muscle in this respect is determined both by the length-tension curve, and by the response of muscle to rapid changes in its mechanical state. In this paper it is shown that the force generated after a small step change in length is related to the dynamical stability of muscle. By means of a simple model, the behavior of isometrically contracting muscle is predicted based on in vitro mechanical studies and classical control theory. It is found that inhomogeneities in sarcomere length can develop only after many seconds, and that this relative stability is due entirely to the presence of the muscle transients.     

Damage to different motor units from active lengthening of the medial gastrocnemius muscle of the cat.

Slow-twitch motor units in the medial gastrocnemius muscle of the anesthetized cat were found to have an average optimum length for active tension that was 0.8 +/- 0.5 (SE) mm longer than the whole muscle optimum. For fast-twitch units (time to peak < 50 ms), the average optimum was 1.3 +/- 0.3 mm shorter than the whole muscle optimum. After the muscle had been subjected to 10 stretches while maximally activated, beginning at the whole muscle optimum length, the optimum lengths of the 27 fast-twitch motor units shifted significantly further in the direction of longer muscle lengths (mean 4.3 +/- 0.3 mm) than for the eight slow-twitch units (2.1 +/- 0.4 mm). A shift in the muscle's length-tension relation was interpreted as being due to sarcomere disruption. Statistical analysis showed that a motor unit's optimum length for a contraction, relative to the whole muscle optimum, was a better indicator of the unit's susceptibility to damage from active lengthenings than was motor unit type.     

Length-tension relation in Limulus striated muscle

Laser diffraction techniques coupled with simultaneous tension measurements were used to determine the length-tension relation in intact, small (0.5-mm thick, 10-mm wide, 20-25-mm long) bundles of a Limulus (horseshoe crab) striated muscle, the telson levator muscle. This muscle differs from the model vertebrate systems in that the thick filaments are not of a constant length, but shorten from 4.9 to approximately 2.0 micrometers as the sarcomeres shorten from 7 to 3 micrometers. In the Limulus muscle, the length-tension relation plateaued to an average maximum tension of 0.34 N/mm2 at a sarcomere length of 6.5 micrometers (Lo) to 8.0 micrometers. In the sarcomere length range from 3.8 to 12.5 micrometers, the muscle developed 50% or more of the maximum tension. When the sarcomere lengths are normalized (expressed as L/Lo) and the Limulus data are compared to those from frog muscle, it is apparent that Limulus muscle develops tension over a relatively greater range of sarcomere lengths.     

Modulation of myocardial stiffness by β-adrenergic stimulation--its role in normal and failing heart

The acute effects of beta-adrenergic stimulation on myocardial stiffness were evaluated. New-Zealand white rabbits were treated with saline (control group) or doxorubicin to induce heart failure (HF) (DOXO-HF group). Effects of isoprenaline (10(-10)-10(-5) M), a non-selective beta-adrenergic agonist, were tested in papillary muscles from both groups. In the control group, the effects of isoprenaline were also evaluated in the presence of a damaged endocardial endothelium, atenolol (beta(1)-adrenoceptor antagonist), ICI-118551 (beta(2)-adrenoceptor antagonist), KT-5720 (PKA inhibitor), L-NNA (NO-synthase inhibitor), or indomethacin (cyclooxygenase inhibitor). Passive length-tension relations were constructed before and after adding isoprenaline (10(-5) M). In the control group, isoprenaline increased resting muscle length up to 1.017+/-0.006 L/L(max). Correction of resting muscle length to its initial value resulted in a 28.5+/-3.1 % decrease of resting tension, indicating decreased muscle stiffness, as confirmed by the isoprenaline-induced right-downward shift of the passive length-tension relation. These effects were modulated by beta(1)- and beta(2)-adrenoceptors and PKA. In DOXO-HF group, the effect on myocardial stiffness was significantly decreased. We conclude that beta-adrenergic stimulation is a relevant mechanism of acute neurohumoral modulation of the diastolic function. Furthermore, this study clarifies the mechanisms by which myocardial stiffness is decreased.     

Muscle and sarcomere lengths in the hind limb of the rabbit (Oryctolagus cuniculus) during a galloping stride

Rabbits were filmed galloping, and the length changes of the principal hind limb muscles were determined. Sarcomere lengths were measured in carcasses set by rigor mortis in four of the positions adopted during a stride. These sarcomere lengths were measured by means of a diffraction technique, devised for the purpose, using an ordinary microscope. Expected sarcomere lengths for three of the positions were predicted from that observed in the fourth, together with muscle length changes. A theoretical length-tension curve for rabbit muscle was constructed, using A and I filament lengths, it was shown that when the muscles were active, their sarcomere lengths corresponded to the plateau of the length-tension curve.     

Canine trachealis muscle shortening and cartilage mechanics.

Canine trachealis muscle will shorten by 70% of resting length when maximally stimulated in vitro. In contrast, trachealis muscle will shorten by only 30-40% when stimulated in vivo. To examine the possibility that an elastic load applied by the tracheal cartilage contributes to the in vivo limitation of shortening, single pairs of sonomicrometry crystals were inserted into the trachealis muscle at the level of the fifth cartilage ring in five dogs. The segment containing the crystals was then excised and mounted on a tension-testing apparatus. Points on the active length-tension curve and the passive length-tension relation of the cartilage only were determined. The preload applied to the muscle before contraction varied from 10 to 40 g (mean 21 +/- 4 g). The afterload applied by the cartilage during trachealis contraction ranged from 13 to 56 g (30 +/- 6 g). The calculated elastic afterloads were substantial and appeared to be sufficient to explain the degree of shortening observed in four of the seven rings; in the remaining three rings, the limitation of shortening was greater than would be expected from the elastic load provided by the cartilage. Additional sources of loading and/or additional mechanisms may contribute to limited in situ shortening. In summary, tracheal cartilage applies a preload and an elastic afterload to the trachealis that are substantial and contribute to the limitation of trachealis muscle shortening in vivo.     

The sarcomere length-tension relation in skeletal muscle

Tension development during isometric tetani in single fibers of frog semitendinosus muscle occurs in three phases: (a) in initial fast-rise phase; (b) a slow-rise phase; and (c) a plateau, which lasts greater than 10 s. The slow-rise phase has previously been assumed to rise out of a progressive increase of sarcomere length dispersion along the fiber (Gordon et al. 1966. J. Physiol. [Lond.]. 184:143--169;184:170-- 192). Consequently, the "true" tetanic tension has been considered to be the one existing before the onset of the slow-rise phase; this is obtained by extrapolating the slowly rising tension back to the start of the tetanus. In the study by Gordon et al. (1966. J. Physiol. [Lond.] 184:170--192), as well as in the present study, the relation between this extrapolated tension and sarcomere length gave the familiar linear descending limb of the length-tension relation. We tested the assumption that the slow rise of tension was due to a progressive increase in sarcomere length dispersion. During the fast rise, the slow rise, and the plateau of tension, the sarcomere length dispersion at any area along the muscle was less than 4% of the average sarcomere length. Therefore, a progressive increase of sarcomere length dispersion during contraction appears unable to account for the slow rise of tetanic tension. A sarcomere length-tension relation was constructed from the levels of tension and sarcomere length measured during the plateau. Tension was independent of sarcomere length between 1.9 and 2.6 microgram, and declined to 50% maximal at 3.4 microgram. This result is difficult to reconcile with the cross-bridge model of force generation.     

Isometric muscle length-tension curves do not predict angle-torque curves of human wrist in continuous active movements

In this study we tested the hypothesis that during steady contractions of human wrist extensors or flexors, the torque-angle relationship during movements imposed about the wrist is predicted by the classical isometric muscle length-tension curve, with ascending, descending and ascending limbs. Angle-torque relationships were measured during steady muscle activation (10% of maximal voluntary contraction: MVC), elicited either by electrical stimulation or voluntary regulation of the electromyogram (EMG). Flexion-extension movements of constant speed (+/-10 degrees /s) were imposed on the subjects' hands with a servo actuator, either through the full physiological range of motion +/-50 degrees, or through +/-10 degrees. During extensor contractions, angle-torque curves in +/-50 degrees movements had ascending, descending and ascending limbs, as in isometric contractions. However, in +/-10 degrees movements, torque always increased with increasing muscle length and decreased with decreasing length, even over angles corresponding to the descending limb of isometric curves. For flexor activation, angle-torque curves had similar properties, though descending limbs were less obvious or absent. During imposed movements, hysteresis was observed in the angle-torque curves. This was attributed to non-linearities of the active muscles. Hysteresis reached a maximum at intermediate wrist angles and declined at maximal muscle length, contradicting the recent hypothesis that sarcomere non-uniformity is responsible for the hysteresis. We conclude that the classical isometric length-tension curve, with its prominent descending limb, does not predict angle-torque curves of human wrist muscles in continuous movements. A more appropriate model is one in which stiffness about the wrist is always positive and hysteresis is a significant factor.     

Length-tension relationship of abdominal expiratory muscles: effect of emphysema

The present study examined the active and passive length-tension relationship of the abdominal expiratory muscles in vitro during electrically stimulated contractions. Studies were performed on isolated strips of transverse abdominis and external oblique muscle from nine adult hamsters with normal lung function. The effect of chronic hyperinflation on the two muscles was assessed in eight hamsters with elastase-induced emphysema. In normal animals the maximal active tension per cross-sectional area (Po) was equal in the two muscles. The absolute muscle fiber length at which Po occurred (Lo) was less for the external oblique than the transverse abdominis and the length-tension curve operated at shorter fiber lengths. However, the change in tension produced by an increase or decrease in muscle length expressed in relative terms (i.e., as %Lo) was greater for the transverse abdominis than the external oblique. Mean total lung capacity of emphysematous animals was 198% of control. Po of the transverse abdominis and external oblique were the same in emphysematous and control animals. However, Lo and the length-tension curve of the transverse abdominis occurred at shorter fiber lengths in emphysematous animals because of a reduction in the number of sarcomeres in series along the fiber. The length-tension curve and the number of sarcomeres in the external oblique was the same in emphysematous and control animals. These results in normal animals indicate that the magnitude of the change in active and passive tension produced by a change in muscle length differs in the transverse abdominis and external oblique. Moreover, chronic hyperinflation of the thorax produced by elastase injection alters the length-tension relationships of some but not all the expiratory muscles.     

Relationship between length-tension relation and 20,000 dalton myosin light chain phosphorylation in guinea-pig taenia caeci

1. Relationship between length-tension relation and phosphorylation of 20,000 dalton myosin light chain (LC20) in guinea-pig taenia caeci was investigated. 2. At in situ length (Lb), a good linear correlation was obtained between isometric tension and LC20 phosphorylation in high-K+-stimulated muscle. 3. In 100 mM K+-stimulated muscle, the active tension decreased at muscle lengths other than Lb, but no significant decrease in degree of LC20 phosphorylation was observed. 4. These results suggest that in guinea-pig taenia caeci, the major portion of the decrease in active tension at muscle lengths other than Lb is not due to a decrease in degree of activation.     

Length-tension relationships are altered in regenerating muscles of the rat after bupivacaine injection.

Intramuscular injection of bupivacaine causes complete degeneration of fibers in extensor digitorum longus (EDL) muscles of rats, followed by complete regeneration within 60 days. Previous studies have shown that regenerated EDL muscles are protected from contraction-induced injury 60 days after bupivacaine injection. It is possible that these regenerated muscles have altered length-tension relations because of fiber remodeling. We tested the hypothesis that length-tension relations are different in bupivacaine-injected and noninjected control muscles. EDL and soleus muscles of the right hindlimb of deeply anesthetized rats were injected with bupivacaine and then allowed to recover for 7, 14, 21, or 60 days (7D, 14D, 21D, 60D), and isometric contractile properties were assessed. Muscles of the contralateral limb were not injected and served as control. EDL muscles recovered from bupivacaine injection more rapidly than soleus muscles, with mass restored to control levels at 21D, and isometric tetanic force (P(o)) restored to control at 60D. In contrast, mass and P(o) of injected soleus muscles was not restored to control even at 60D. In 7D EDL muscles, length-tension curves were shifted leftward compared with control, but in 21D and 60D EDL muscles length-tension curves were right shifted significantly (treatment x muscle length: P < 0.001). Although no clear shift in the position of the length-tension curve was observed in regenerating soleus muscles, force production was enhanced on the descending limb of the curve in 60D soleus muscles (treatment x relative muscle length: P < 0.01). The rightward shift in the length-tension curve of EDL muscles 60 days after bupivacaine injection is likely to contribute to the mechanism for their previously observed protection from contraction-induced injury.     

Rest length and compliance of non-immobilised and immobilised rabbit soleus muscle and tendon

The first aim of this study was to measure the contributions of muscle and tendon to the total compliance of resting muscle-tendon units. A second aim was to determine whether the decrease in muscle-tendon unit rest length produced by prolonged immobilisation in a shortened position is mediated primarily by adaptations of the muscle or tendon. One ankle joint from each of five rabbits was immobilised in a plantarflexed position for 14 days. The passive length-tension properties of soleus muscle fascicles and tendons from both hindlimbs were measured using a video-based tensile-testing system. In non-immobilised muscles, muscle fascicle strains exceeded tendon strains by up to four times. However, because the rest length of tendon was much greater than that of muscle fascicles, changes in tendon length accounted for nearly half of the total change in muscle-tendon unit length. The rest length of immobilised muscle-tendon units was less than that of non-immobilised muscle-tendon units from contralateral limbs. Most of this difference was attributable to a change in the rest length of the tendon; there was little change in the rest length of muscle fascicles. It is concluded that the tendon is responsible for a large part of the compliance of rabbit soleus muscle-tendon units at physiological resting tensions, and that adaptation of tendon rest length is the primary mechanism by which the rabbit soleus shortens in response to immobilisation at short lengths. Accepted: 7 May 1997     

Model of muscle-tendon interaction during frog semitendinosis fixed-end contractions.

A structural model was developed to explain sarcomere shortening at the expense of tendon lengthening in the frog semitendinosis (ST) muscle-tendon system. The model was based on the data of Lieber et al. [Am. J. Physiol. 261, C86-C92 (1991)], who determined the relationship between the sarcomere length, tendon load (as a fraction of maximum isometric tension) and tendon, bone-tendon junction (BTJ), and aponeurosis strain. The model was generated assuming a finite time-course of cross-bridge attachment [Huxley, Prog. Biophys. 7,255-318 (1957)], an ideal sarcomere length-tension relationship [Gordon et al., J. Physiol. 184, 170-192 (1966)] and an ideal force-velocity relationship [Katz, J. Physiol. 96, 45-64 (1939); Edman, J. Physiol. 291, 143-159 (1979)]. Functionally, sarcomeres operated on three distinct regions of the length-tension curve: (1) regions where the muscle force decreased as sarcomeres shortened (the shallow and steep ascending limbs); (2) regions where the muscle force increased as sarcomeres shortened and there was little passive tension (descending limb, where sarcomere length greater than or equal to 3.0 microns); and (3) regions where the muscle force increased as sarcomeres shortened and there was a significant passive tension (descending limb where sarcomere length greater than 3.0 microns). Using such a physiological model, it was found that the effect of tendon compliance was to 'skew' the sarcomere length-tension curve to the right and to increase the operating range of the muscle-tendon unit.(ABSTRACT TRUNCATED AT 250 WORDS)     

Whole muscle length-tension relationships are accurately modeled as scaled sarcomeres in rabbit hindlimb muscles

An a priori model of the whole active muscle length-tension relationship was constructed utilizing only myofilament length and serial sarcomere number for rabbit tibialis anterior (TA), extensor digitorum longus (EDL), and extensor digitorum II (EDII) muscles. Passive tension was modeled with a two-element Hill-type model. Experimental length-tension relations were then measured for each of these muscles and compared to predictions. The model was able to accurately capture the active-tension characteristics of experimentally-measured data for all muscles (ICC=0.88 ± 0.03). Despite their varied architecture, no differences in predicted versus experimental correlations were observed among muscles. In addition, the model demonstrated that excursion, quantified by full-width-at-half-maximum (FWHM) of the active length-tension relationship, scaled linearly (slope=0.68) with normalized muscle fiber length. Experimental and theoretical FWHM values agreed well with an intraclass correlation coefficient of 0.99 (p<0.001). In contrast to active tension, the passive tension model deviated from experimentally-measured values and thus, was not an accurate predictor of passive tension (ICC=0.70 ± 0.07). These data demonstrate that modeling muscle as a scaled sarcomere provides accurate active functional but not passive functional predictions for rabbit TA, EDL, and EDII muscles and call into question the need for more complex modeling assumptions often proposed.     

Rises in whole muscle passive tension of mammalian muscle after eccentric contractions at different lengths.

This is a report of experiments carried out on the medial gastrocnemius muscle of the anesthetized cat, investigating the effects of eccentric contractions carried out at different muscle lengths on the passive and active length-tension relationships. In one series of experiments, the motor supply to the muscle was divided into three approximately equal parts; in the other, whole muscles were used. Fifty eccentric contractions were carried out over different regions of the active length-tension curve for each partial or whole muscle. Active and passive length-tension curves were measured before and after the eccentric contractions. When eccentric contractions were carried out at longer lengths, there was a larger shift of the optimum length for active tension in the direction of longer muscle lengths and a larger fall in peak isometric tension. Passive tension was higher immediately after the eccentric contractions, and if the muscle was left undisturbed for 40 min, it increased further to higher values, particularly after contractions at longer lengths. A series of 20 passive stretches of the same speed and amplitude and covering the same length range as the active stretches, reduced the passive tension which redeveloped over a subsequent 40-min period. It is hypothesized that there are two factors influencing the level of passive tension in a muscle after a series of eccentric contractions. One is injury contractures in damaged muscle fibers tending to raise passive tension; the other is the presence of disrupted sarcomeres in series with still-functioning sarcomeres tending to reduce it.     

A mathematical analysis of the force-stiffness characteristics of muscles in control of a single joint system

Feldman (1966) has proposed that a muscle endowed with its spinal reflex system behaves as a non-linear spring with an adjustable resting length. In contrast, because of the length-tension properties of muscles, many researchers have modeled them as non-linear springs with adjustable stiffness. Here we test the merits of each approach: Initially, it is proven that the adjustable stiffness model predicts that isometric muscle force and stiffness are linearly related. We show that this prediction is not supported by data on the static stiffness-force characteristics of reflexive muscles, where stiffness grows non-linearly with force. Therefore, an intact muscle-reflex system does not behave as a non-linear spring with an adjustable stiffness. However, when the same muscle is devoid of its reflexes, the data shows that stiffness grows linearly with force. We aim to understand the functional advantage of the non-linear stiffness-force relationship present in the reflexive muscle. Control of an inverted pendulum with a pair of antagonist muscles is considered. Using an active-state muscle model we describe force development in an areflexive muscle. From the data on the relationship of stiffness and force in the intact muscle we derive the length-tension properties of a reflexive muscle. It is shown that a muscle under the control of its spinal reflexes resembles a non-linear spring with an adjustable resting length. This provides independent evidence in support of the Feldman hypothesis of an adjustable resting length as the control parameter of a reflexive muscle, but it disagrees with his particular formulation. In order to maintain stability of the single joint system, we prove that a necessary condition is that muscle stiffness must grow at least linearly with force at isometric conditions. This shows that co-contraction of antagonist muscles may actually destabilize the limb if the slope of this stiffness-force relationship is less than an amount specified by the change in the moment arm of the muscle as a function of joint configuration. In a reflexive muscle where stiffness grows faster than linearly with force, co-contraction will always lead to an increase in stiffness. Furthermore, with the reflexive muscles, the same level of joint stiffness can be produced by much smaller muscle forces because of the non-linear stiffness-force relationship. This allows the joint to remain stable at a fraction of the metabolic energy cost associated with maintaining stability with areflexive muscles.This work was supported in part by grant no. 1R01 NS 24926 from the NIH (Michael Arbib, PI). R.S. was supported by an IBM Graduate Fellowship in Computer Science     

A comparison of two Hill-type skeletal muscle models on the construction of medial gastrocnemius length-tension curves in humans in vivo

Human length-tension curves are traditionally constructed using a model that assumes passive tension does not change during contraction (model A) even though the animal literature suggests that passive tension can decrease (model B). The study's aims were threefold: 1) measure differences in human medial gastrocnemius length-tension curves using model A vs. model B, 2) test the reliability of ultrasound constructed length-tension curves, and 3) test the robustness of fascicle length-generated length-tension curves to variations between the angle and fascicle length relationship. An isokinetic dynamometer manipulated and measured ankle angle while ultrasound was used to measure medial gastrocnemius fascicle length. Supramaximal tibial nerve stimulation was used to evoke resting muscle twitches. Length-tension curves were constructed using model A {angle-torque [A-T((A))], length-torque [L-T((A))]} or model B {length-torque [L-T((B))]} in three conditions: baseline, heel-lift (where the muscle was shortened at each angle), and baseline repeated 2 h later (+2 h). Length-tension curves constructed from model B differed from those produced via model A, indicated by a significant increase in maximum torque (≈23%) when using L-T((B)) vs. L-T((A)). No parameter measured was different between baseline and +2 h for any method, indicating good reliability when using ultrasound. Length-tension curves were unaffected by the heel-lift condition when using L-T((A)) or L-T((B)) but were affected when using A-T((A)). Since the muscle model used significantly alters human length-tension curves, and given animal data indicate model B to be more accurate when passive tension is present, we recommend that model B should be used when constructing medial gastrocnemius length-tension curves in humans in vivo.     

The effect of rate, paired pacing and calcium on the length-tension relations in the rabbit papillary muscle

The effect of sustained paired pacing, extracellular Ca2+ concentration and of the rate of steady-state single pacing on the length-tension relations in the isolated papillary muscles of right ventricles of rabbit hearts was investigated. We found that full range change of contractile force (CF, from close to zero to maximal) may be obtained by means of the change of the resting muscle length by 10-15% of Lmax (the length at which CF is maximal). This change brings about the shift of the thin filaments of the sarcomeres along the thick ones by one sixth of their length. The only effect of all the applied interventions could be reproduced by multiplying CF at each length step by some coefficient. Neither of them did change the basic pattern of length-tension relations. These results are compatible with the hypothesis that the basic mechanism of length-tension relations is the change of sensitivity of contractile system to the sarcoplasmic Ca2+ concentration.     

Dependence of the length-tension relationship on agonist concentration in vascular smooth muscle

This study examines the dependence of the length-tension (L-T) relationship in vascular smooth muscle on its level of activation. A horizontal shift of the L-T relationship with a change in activation level has been shown in striated muscle when L-T curves could not be superimposed. Active force at each length was normalized to the maximum active force in each curve. Indices of a horizontal shift of a L-T curve include the initial length for an active response (Li) and the length for maximum active force (Lmax). In this study normalized L-T curves were obtained from rings of the dog anterior tibial artery at low (approximately ED50) and high (maximal activation) concentrations of potassium (K+), norepinephrine (NE), and calcium (Ca2+). The normalized curve with a low concentration of K+ or NE was shifted to the right of the curve obtained with a high concentration. Li and Lmax were significantly longer for a low concentration of K+ or NE than a high concentration. With the same concentration of NE (10(-5) M) no difference in the normalized L-T curves, in Li, or in Lmax were found when low (0.085 mM) Ca2+ experiments were compared to normal (1.7 mM) Ca2+ experiments. It may be concluded that the length-tension relationship in vascular smooth muscle is shifted to longer lengths with a decrease in the concentration of a chemical agonist but not by a decrease in external calcium. We suggest that a concentration dependent shift in the length-tension relationship may have a role in the regulation of blood flow.