Passive Length-tension Curves Research Articles

Surgical Mobilization of Skeletal Muscles Changes Functional Properties—Implications for Tendon Transfers

Tendon transfer surgery restores function by rerouting working muscle-tendon units to replace the function of injured or paralyzed muscles. This procedure requires mobilizing a donor muscle relative to its surrounding myofascial connections, which improves the muscle's new line of action and increases excursion. However, the biomechanical effect of mobilization on a donor muscle's force-generating function has not been previously studied under invivo conditions. The purpose of this study was to quantify the effect of surgical mobilization on active and passive biomechanical properties of 3 large rabbit hind limb muscles. Myofascial connections were mobilized stepwise from the distal end to the proximal end of muscles (0%, 25%, 50%, and 75% of muscle length) and their active and passive length-tension curves were measured after each degree of mobilization. Second toe extensor, a short-fibered muscle, exhibited a 30% decline in peak stress and 70% decline in passive stress, whereas extensor digitorum longus, a short-fibered muscle, and tibialis anterior, a long-fibered muscle, both exhibited similar smaller declines in active (about 18%) and passive stress (about 65%). The results highlight 3 important points: (1) a trade-off exists between increasing muscle mobility and decreasing force-generating capacity; (2) intermuscular force transmission is important, especially in second toe extensor, because it was able to generate 70% of its premobilization active force although most fibers were freed from their native origin; and (3) muscle architecture is not the major influence on mobilization-induced force impairment. These data demonstrate that surgical mobilization itself alters the passive and active force-generating capacity of skeletal muscles. Thus, surgical mobilization should not be viewed simply as a method to redirect the line of action of a donor muscle because this procedure has an impact on the functional properties of the donor muscle itself.

The MyoRobot: A novel automated biomechatronics system to assess voltage/Ca2+ biosensors and active/passive biomechanics in muscle and biomaterials

We engineered an automated biomechatronics system, MyoRobot, for robust objective and versatile assessment of muscle or polymer materials (bio-)mechanics. It covers multiple levels of muscle biosensor assessment, e.g. membrane voltage or contractile apparatus Ca2+ ion responses (force resolution 1µN, 0–10mN for the given sensor; [Ca2+] range ~ 100nM–25µM). It replaces previously tedious manual protocols to obtain exhaustive information on active/passive biomechanical properties across various morphological tissue levels. Deciphering mechanisms of muscle weakness requires sophisticated force protocols, dissecting contributions from altered Ca2+ homeostasis, electro-chemical, chemico-mechanical biosensors or visco-elastic components. From whole organ to single fibre levels, experimental demands and hardware requirements increase, limiting biomechanics research potential, as reflected by only few commercial biomechatronics systems that can address resolution, experimental versatility and mostly, automation of force recordings. Our MyoRobot combines optical force transducer technology with high precision 3D actuation (e.g. voice coil, 1µm encoder resolution; stepper motors, 4µm feed motion), and customized control software, enabling modular experimentation packages and automated data pre-analysis. In small bundles and single muscle fibres, we demonstrate automated recordings of (i) caffeine-induced-, (ii) electrical field stimulation (EFS)-induced force, (iii) pCa-force, (iv) slack-tests and (v) passive length-tension curves. The system easily reproduces results from manual systems (two times larger stiffness in slow over fast muscle) and provides novel insights into unloaded shortening velocities (declining with increasing slack lengths). The MyoRobot enables automated complex biomechanics assessment in muscle research. Applications also extend to material sciences, exemplarily shown here for spider silk and collagen biopolymers.

Gastrocnemius Muscle Contracture After Spinal Cord Injury

The aim of this study was to examine changes in passive length and stiffness of the gastrocnemius muscle-tendon unit in people after spinal cord injury. In a prospective longitudinal study, eight wheelchair-dependent participants with severe paralysis were assessed 3 and 12 mos after spinal cord injury. Passive torque-angle data were obtained as the ankle was slowly rotated through range at six knee angles. Differences in passive ankle torque-angle data recorded at different knee angles were used to derive passive length-tension curves of the gastrocnemius muscle-tendon unit. Ultrasound imaging was used to determine fascicle and tendon contributions to the muscle-tendon unit length-tension curves. The participants had ankle contractures (mean [SD] maximum passive ankle dorsiflexion angle, 88 [9] degrees) 3 mos after spinal cord injury. Ankle range did not worsen significantly during the subsequent 9 mos (mean change, -5 degrees; 95% confidence interval, -16 to 6 degrees). There were no changes in the mean slack length or the stiffness of the gastrocnemius muscle-tendon unit or in the slack lengths of the fascicles or the tendon between 3 and 12 mos after spinal cord injury. There were no consistent patterns of the change in slack length or stiffness with the changes in ankle range in the data from the individual participants. This study, the first longitudinal study of muscle length and stiffness after spinal cord injury, showed that the length and the stiffness of the gastrocnemius did not change substantially between 3 and 12 mos after injury.

Muscle excursion does not correlate with increased serial sarcomere number after muscle adaptation to stretched tendon transfer

Chronic skeletal muscle stretch typically increases serial muscle fiber sarcomere number. Since serial sarcomere number correlates with functional excursion in normal muscle, observed changes in sarcomere number are often extrapolated to their new assumed function. However, this has not been well demonstrated experimentally. Thus, we measured the functional properties of muscles stretched due to tendon transfer surgery. Muscle active and passive length-tension curves were measured 1 week and 4 weeks after surgery, and then each muscle was further examined to determine structural adaptation as well as single fiber and fiber bundle passive mechanical properties. We found a disconnect between the functional and structural muscle properties. Specifically, muscle excursion was significantly lower in the transferred muscle compared to controls, even though serial sarcomere number had increased. Furthermore, maximum tetanic tension was significantly reduced, though the two groups had similar physiological cross sectional areas. Passive tension increased in the transferred muscle, which was deemed to be due to proliferation of extracellular matrix. These data are the first to report that muscle morphological adaptation after chronic stretch does not accurately predict the muscle's functional properties. These data have significant implications for examining muscle physiological properties under surgical interventions.

Length adaptation of the active length‐tension curve in rabbit detrusor smooth muscle

Until the 1990s, the active and passive length‐tension (L‐T) curves for smooth muscle were believed to be static, with single passive tension (Tp) and maximum active tension (Ta) values for each length. However, recent studies have shown that the L‐Ta curves in airway and vascular smooth muscles can adapt to length changes. Our prior studies have shown that the L‐Tp curve in detrusor smooth muscle (DSM) is not static and can shift along the length axis as a function of strain and activation history, a trait we labeled adjustable passive stiffness (APS). In the present study, calcium‐free Tp and peak total tension (Tt) during a maximal KCl‐induced contraction were measured in DSM strips, and Ta was found by subtracting Tp from Tt. Strips were contracted at their passive slack length (Ls, ~3 mm) and then passively stretched to and contracted 5 times at 3‐fold Ls. These contractions produced increasingly greater Ta that approached a steady value. Next, strips were contracted once at 4‐fold Ls, returned to 3‐fold Ls and contracted 5 times. Ta at 3‐fold Ls was reduced after the contraction at 4‐fold Ls, and the 4 subsequent contractions at 3‐fold Ls produced increasingly greater Ta that returned to the initial steady Ta. These results provide evidence that the L‐Ta curve in DSM can adapt to changes in length. Support was provided by the Edwin Beer Research Program in Urology and Urology‐Related Fields of The New York Academy of Medicine.

Myometrial mechanoadaptation during pregnancy: implications for smooth muscle plasticity and remodelling

The smooth muscle of the uterus during pregnancy presents a unique circumstance of physiological mechanotransduction as the tissue remodels in response to stretches imposed by the growing foetus(es), yet the nature of the molecular and functional adaptations remain unresolved. We studied, in myometrium isolated from non-pregnant (NP) and pregnant mice, the active and passive length–tension curves by myography and the expression and activation by immunoblotting of focal adhesion-related proteins known in other systems to participate in mechanosensing and mechanotransduction. In situ uterine mass correlated with pup number and weight throughout pregnancy. In vitro myometrial active, and passive, length-tension curves shifted significantly to the right during pregnancy indicative of altered mechanosensitivity; at term, maximum active tension was generated following 3.94 ± 0.33-fold stretch beyond slack length compared to 1.91 ± 0.12-fold for NP mice. Moreover, mechanotransduction was altered during pregnancy as evidenced by the progressive increase in absolute force production at each optimal stretch. Pregnancy was concomitantly associated with an increased expression of the dense plaque-associated proteins FAK and paxillin, and elevated activation of FAK, paxillin, c-Src and extracellular signal-regulated kinase (ERK1/2) which reversed 1 day post-partum. Electron microscopy revealed close appositioning of neighbouring myometrial cells across a narrow extracellular cleft adjoining plasmalemmal dense plaques. Collectively, these results suggest a physiological basis of myometrial length adaptation, long known to be a property of many smooth muscles, whereupon plasmalemmal dense plaque proteins serve as molecular signalling and structural platforms contributing to functional (contractile) remodelling in response to chronic stretch.

The significance of variable passive compliance in smooth muscle

anyone contemplating dynamic roentgenograms of hollow viscera must be impressed that the length changes in the smooth muscles that comprise their walls are larger than the threefold range produced by skeletal muscle having a fixed filament array ([1][1]), and studies of muscles isolated from these

Adjustable passive length-tension curve in rabbit detrusor smooth muscle

Until the 1990s, the passive and active length-tension (L-T) relationships of smooth muscle were believed to be static, with a single passive force value and a single maximum active force value for each muscle length. However, recent studies have demonstrated that the active L-T relationship in airway smooth muscle is dynamic and adapts to length changes over a period of time. Furthermore, our prior work showed that the passive L-T relationship in rabbit detrusor smooth muscle (DSM) is also dynamic and that in addition to viscoelastic behavior, DSM displays strain-softening behavior characterized by a loss of passive stiffness at shorter lengths following a stretch to a new longer length. This loss of passive stiffness appears to be irreversible when the muscle is not producing active force and during submaximal activation but is reversible on full muscle activation, which indicates that the stiffness component of passive force lost to strain softening is adjustable in DSM. The present study demonstrates that the passive L-T curve for DSM is not static and can shift along the length axis as a function of strain history and activation history. This study also demonstrates that adjustable passive stiffness (APS) can modulate total force (35% increase) for a given muscle length, while active force remains relatively unchanged (4% increase). This finding suggests that the structures responsible for APS act in parallel with the contractile apparatus, and the results are used to further justify the configuration of modeling elements within our previously proposed mechanical model for APS.

Length-tension relationship of the feline thyroarytenoid muscle

Vocal fold tension during phonation is generated by coordinated contraction of the intrinsic laryngeal muscles. The thyroarytenoid muscle has been found to have increased stiffness at various levels of strain when compared with other intrinsic laryngeal muscles. The objective here is to test the hypothesis that the thyroarytenoid muscle exhibits high passive tension during maximal isometric tetanic force generation, and to test the hypothesis that the thyroarytenoid maintains the ability to generate contractile force at high levels of strain more effectively than other skeletal muscle. The thyroarytenoid muscles (n = 9) and digastric muscle strips (n = 7) were removed from adult random-bred cats. Maximal isometric tension and passive tension at optimum length were measured from each muscle in vitro. Active and passive length-tension curves were constructed for each muscle. The contractile properties of the thyroarytenoid group were compared with those of the digastric muscle group. The thyroarytenoid muscle group required on average 140 mN of passive tension to generate maximal isometric tetanic tension. This represented 39% of the average maximal isometric tetanic tension generated by the muscles. These results were significantly higher than the digastric muscle group, which required on average 28 mN of passive tension (9% of maximal isometric tetanic tension, p<0.05). At 110% of optimum length, the thyroarytenoid muscle maintained 89.8% of maximal isometric tetanic force, whereas the digastric muscle group maintained 67.7% of maximal isometric tetanic force ( p<0.05). The thyroarytenoid muscle exhibits higher passive tension when generating maximal isometric tension than the digastric muscle control group. The thyroarytenoid muscle maintains higher levels of active tension at high strain than the digastric muscle control group. We conclude that these findings are related to the ability of the thyroarytenoid muscle to function as a fine tensor of the vocal fold in a high strain environment.

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.

Essential role of L-arginine uptake and protein tyrosine kinase activity for NO-dependent vasorelaxation induced by stretch, isometric tension and cyclic AMP in rat pulmonary arteries.

1. The NO-dependent component of cyclic AMP-induced vasorelaxation in rat pulmonary arteries is critically dependent on extracellular L-arginine but independent of endothelial cell intracellular [Ca(2+)]. We examined whether L-arginine uptake was also essential for NO production induced by passive stretch or isometric tension, processes also reported to be Ca(2+)-independent. 2. The passive length-tension curve was depressed by physiological concentrations of L-arginine (400 microM; P<0.05). Inhibition of the y(+) transporter with 10 mM L-lysine, NO synthase with L-NAME (100 microM), or protein tyrosine kinase with erbstatin A (30 microM) caused identical upward shifts (P<0.001), alone or in combination. Tyrphostin 23 was similar to erbstatin A, whilst the inactive analogue tyrphostin A1 and genistein were without effect. 3. L-arginine (400 microM) shifted the PGF(2 alpha) concentration-response curve under isometric conditions to the right (P<0.05), whereas L-NAME or L-lysine caused a leftward shift (P<0.001). Tyrphostin 23 (30 microM) more than reversed the L-arginine-induced suppression of PGF(2 alpha)-induced tension; subsequent addition of L-NAME had no effect. The L-lysine-sensitive component of CPT cyclic AMP-induced vasorelaxation was abolished by erbstatin A. 4. ACh-induced vasorelaxation was approximately 80% inhibited by L-NAME, but was not affected by L-lysine or 400 microM L-arginine. Erbstatin A reduced the vasorelaxation by only approximately 25%. 5. We conclude that activation of NO production by stretch, isometric tension, or cyclic AMP in rat pulmonary arteries is critically dependent on the presence and uptake of physiological concentrations of extracellular L-arginine, and protein tyrosine kinase activity. This directly contrasts with ACh-induced vasorelaxation, which was independent of extracellular L-arginine, and relatively unaffected by tyrosine kinase inhibition.

Is the spring quality of muscle plastic?

During locomotion, major muscle groups are often activated cyclically. This alternate stretch-shorten pattern of activity could enable muscle to function as a spring, storing and recovering elastic recoil potential energy. Because the ability to store and recover elastic recoil energy could profoundly affect the energetics of locomotion, one might expect this to be an adaptable feature of skeletal muscle. This study tests the hypothesis that chronic eccentric (Ecc) training results in a change in the spring properties of skeletal muscle. Nine female Sprague-Dawley rats underwent chronic Ecc training for 8 wk on a motorized treadmill. The spring properties of muscle were characterized by both active and passive lengthening force productions. A single "spring constant (Deltaforce/Deltalength) from the passive length-tension curves was calculated for each muscle. Results from measurements on long heads of triceps brachii muscle indicate that the trained group produced significantly more passive lengthening force (P = 0.0001) as well as more active lengthening force (P = 0.0001) at all lengths of muscle stretch. In addition, the spring constants were significantly different between the Ecc (1.71 N/mm) and the control (1.31 N/mm) groups. A stiffer spring is capable of storing more energy per unit length stretched, which is of functional importance during locomotion.

Length-tension Properties of Extraocular Muscles in Patients with Esotropia and Intermittent Exotropia

The purpose of this study was to determine the passive length-tension characteristics of horizontal recti muscles in patients with non-restrictive horizontal strabismus. A system to measure intraoperative continuous-registration passive length-tension curves of detached extraocular muscles was designed. The size of the preoperative deviation and the change in the deviation as a result of surgery was correlated with the passive tension of the medial rectus muscle in patients with acquired esotropia. Patients with infantile esotropia or intermittent exotropia showed no relationship between passive tension and either preoperative deviation or response to surgery. Surgical recession of both the medial and lateral recti muscles produced large changes in the passive tension characteristics of both of these muscles. Medial rectus muscle recession produced larger changes in the passive tension than equal amounts of recession of lateral recti muscles.

Active tension generation in isolated skeletal myofibrils.

Single or double myofibrils isolated from rabbit psoas muscle were suspended between a fine needle and an optical force transducer. By using a photodiode array, the length of every sarcomere along the specimen could be measured. Relaxed specimens exhibited uniform sarcomere lengths and their passive length-tension curve was comparable to that of larger specimens. Most specimens could be activated and relaxed four to five times before active force levels began to decline; some specimens lasted for 10-15 activation cycles. Active tension (20-22 degrees C) was reproducible from contraction to contraction. The contractile response was dependent on initial sarcomere length. If initially activated at sarcomere lengths of > or = 2.7 microns, one group of sarcomeres usually shortened to sarcomere lengths of 1.8-2.0 microns, while the remaining sarcomeres were stretched to longer lengths. Myofibrils that were carefully activated at shorter initial sarcomere lengths usually contracted homogeneously. Both homogeneous and inhomogeneous contractions produced high levels of active tension. Calcium sensitivity was found to be comparable to that in larger preparations; myofibrils immersed in pCa 6.0 solution generated 30% of maximal tension, while pCa 5.5-4.5 resulted in full activation. Active tension at full overlap of thick and thin filaments ranged from 0.34 to 0.94 N mm-2 (mean of 0.59 N mm-2 +/- 0.13 SD. n = 65). Even allowing for a maximum of 20% nonmyofibrillar space in skinned or intact muscle fibres, the mean tension generated by isolated myofibrils per cross-sectional area is higher than by fibre preparations.

Urinary Bladder Function in the Tight-Skin Mouse

Tight-skin mice develop hypertrophy of connective tissue and tendons, associated with increases in collagen concentration in skin, heart, lungs, and tail. The bladders from these mice have not previously been examined. Because of the purported importance of collagen in bladder wall structure and compliance, we examined collagen content, micturition characteristics, and length-tension relationships in bladders from tight-skin mice. Bladder collagen content and concentration were approximately 70% greater in 5-6 month tight-skin mice than age-matched controls, but bladder mass, protein content, and protein concentration were similar. Tight-skin mice urinated larger volumes more frequently during the light cycle, and the functional bladder capacity appeared to be greater than that of controls. There was a small shift to the right of the passive length-tension curves of bladder strips from tight-skin mice, but the shift was not statistically significant. The magnitude of active tension development was the same. The data suggest that bladder collagen concentration does not necessarily determine bladder capacity or compliance. It is suggested that other factors, such as the ratio of collagen subtypes or the collagemelastin ratio may have more importance for the maintenance of bladder distension.

Calcium sensitivity of isometric tension in intact papillary muscles and chemically skinned trabeculae in different models of hypertensive hypertrophy

STUDY OBJECTIVE - The aim was to examine the contractile state, the inotropic response to [Ca2+]e and the Ca2+ sensitivity of the contractile proteins in different models of hypertensive hypertrophy in an early stage of evolution (3-4 weeks). DESIGN - Renal hypertension was induced by placing a silver clip around the left renal artery. The contralateral kidney was either removed (1K-1C) or left untouched (2K-1C). Hypertension through sodium overload was produced by administration of deoxycorticosterone and 1% NaCl drinking water. (DOCA rats). Active and passive length-tension curves were performed to evaluate basal contractility at Lmax and passive stiffness of cardiac muscle. The inotropic responsiveness to [Ca2+]e and the Ca2+ sensitivity of the contractile proteins were also evaluated. EXPERIMENTAL MATERIAL - Papillary muscles and skinned trabeculae from the left ventricle of male Wistar hypertensive and age matched normotensive rats were used. MEASUREMENTS AND RESULTS - Cardiac hypertrophy was similar in all hypertensive groups. In 2K-1C and 1K-1C rats, basal contractility was not significantly different from controls. In DOCA rats, developed tension and time to peak tension (TTP) were significantly greater than controls. The inotropic response to [Ca2+]e was depressed in 2K-1C and increased in DOCA rats. In DOCA rats, increasing [Ca2+]e produced an increase in TTP greater than in controls. No differences were detected in muscle passive stiffness or in Ca2+ sensitivity of the contractility proteins among the different groups. CONCLUSIONS - In the earlier stages of hypertensive hypertrophy, differences in basal contractile state and/or inotropic responsiveness appear to be more related to the initiating cause of hypertensive hypertrophy than to the degree of hypertrophy itself. These differences cannot be attributed to changes in Ca2+ sensitivity of the contractile system.

Length-tension relationship of striated muscle of cat external anal sphincter.

The active and passive length-tension curves of small strips of cat external anal sphincter (EAS) were examined in vitro. The striated muscle fibers were arranged perpendicular to the long axis of the longitudinal smooth muscle cells of the longitudinal layer of the anal canal. Histological examination indicated that the strips were comprised of striated muscle fibers oriented in the long axis of the strip. Electrical field stimulation elicited twitch and tetanus responses that were not altered by the administration of gallamine triethiodide (10(-6) to 10(-4) M), a neuromuscular blocking agent. At 37 degrees C the time from the onset of the twitch contraction to the development of peak force ranged from 30 to 37 ms, the time from peak force to one-half relaxation ranged from 20 to 25 ms. The maximum active twitch and tetanus tension (Po) averaged 0.23 and 0.90 kg/cm2, respectively. Active tension could be developed over a range of 0.6-1.4 optimum length (Lo). The passive length-tension curve showed that the muscle had significant passive tension at lengths below the Lo for tension development and a high passive tension at Lo (average of 44% of active isometric twitch tension, 12.2% of active isometric tetanus tension) and above Lo. We conclude that the passive length-tension curve for the EAS is stiffer than that of typical mammalian skeletal muscles. We suggest that this difference is related to the adaptation of the EAS to its sphincteric function as a component of a hollow organ.

Relaxation-induced contraction of smooth muscle surrounding hamster ovarian follicles.

Changes in intrafollicular pressure and follicular diameter resulting from injecting or withdrawing fluid from the antrum were measured in preovulatory follicles and used as an assay for changes in tension in the follicular wall by applying the Laplace relationship for thin-walled spheres. Passive length-tension curves were constructed from pressure-volume measurements to establish baseline wall stiffness. Any subsequent change in pressure could then be compared to the length-tension curves to evaluate whether it arose from active tension development or from passive stretch. When intact follicles (1-2h before ovulation) were subjected to release of passive stretch, they exhibited a contractile response that lasted 15 sec-2 min and was characterized by cyclic increases and decreases in tension, with a period of 1 cycle every 2-3 sec. The probability of activating a response in the tissue was most strongly correlated with the rate of release of passive stretch. Intrafollicular pressures generated during active contractile responses sometimes reached 80 mmHg (10.64 mPa), corresponding to a wall tension of 5332 dynes/cm (5.332 N/m) (for a 1 mm follicle) and were clearly well above the passive length-tension curves. Passive stretching of the follicular wall during a contractile response to 5-hydroxytryptamine stimulation resulted in large reductions in active wall tension for the duration of the stretch. These results are consistent with a stretch-activated inhibition of contractile events.

Calcium-dependent resistance to stretch and stress relaxation in resting smooth muscles

Mechanical responses to stretch and length-tension relations were examined in rabbit taenia coli, mesenteric vein, aorta, and myometrium and in guinea pig taenia coli made atonic by incubation in Krebs-bicarbonate solution at 20-22 degrees C. When stretched 10% of the length at which maximum active tension is observed (Lo) in 0.5 s, the muscles showed a transient large force (resistance to stretch) that decayed to a new constant level within minutes (stress relaxation). The resistance to stretch decreased markedly in Ca2+-free [disodium ethylene glycolbis-(beta-aminoethylether)-N,N-tetraacetic acid (EGTA)] Krebs but was restored in normal Krebs solution. Calcium removal did not affect the passive length-tension curve. The absence of Ca2+ did not change the steady-state force maintained by the muscle; thus stretch resistance was not due to tone. Blockade of Ca2+ influx associated with electrical activity with 5-[3,4-dimethoxyphenethyl)methylamino]-2-(3,4,5-trimethoxyphenyl-2-isopropylvaleronitrile (D-600) and of Ca2+ release from intracellular sites with thymol (1 mM) completely blocked contraction but did not alter the responses to stretch, thus dissociating the responses to stretch from these processes and tension development. The Ca2+-dependent stress relaxation showed a dependence on muscle length similar to that for active tension development. Except at long muscle lengths, where connective tissue markedly affects length-tension relations, most of the "viscoelasticity" of these smooth muscles is dependent on calcium and may be largely due to the straining of crossbridges that are attached, but not generating a net force, in the resting state.

Length-tension relationship of smooth muscle of the hog carotid artery.

The length-tension relationships for arterial smooth muscle were determined using vascular strips teased from the media of hog carotid arteries. Histological examination revealed that the strips were (1) free of adventitia and (2) composed of smooth muscle cells oriented parallel to the long axis of the strips. Measurements from electron micrographs indicated that 60% of the cross-sectional area consisted of smooth muscle. At L 0 (the optimal length for tension development) the total cross-sectional area of the strips varied from 0.3 to 0.8 mm 2 . Potassium-induced depolarization was the most effective stimulus for force development. Norepinephrine and electric field stimulation elicited responses which were 70% and 30%, respectively, of that produced by potassium-induced depolarization. At L 0 the intrinsic load-bearing capacity (P 0 ) of the contractile system was 2.22 x 10 6 dynes/cm 2 . Tension development fell off gradually at lengths shorter than L 0 and more rapidly at lengths greater than L 0 . Passive length-tension curves were determined after quick releases from higher to lower lengths to avoid complications arising from tone. Passive tension was negligible at lengths below 0.9 L 0 . At L 0 the passive tension was 10% of P 0 .