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Contraction history modulates isotonic shortening velocity in smooth muscle.

The effect of contraction history on the isotonic shortening velocity of canine tracheal smooth muscle was investigated. Muscles were contracted isometrically for 20 s at initial lengths of L(o) (length of maximal active force), 85% L(o), or 70% L(o) using electrical field stimulation. Muscles were then allowed to shorten isotonically under different afterloads either with or without first being subjected to a step decrease in length to 70% L(o). Instantaneous velocities were plotted against instantaneous muscle length during isotonic shortening. Regardless of protocol, the velocity at any muscle length during shortening was lower when the muscle was initially activated at a longer length. The isotonic shortening velocity decreased progressively during shortening at a nearly linear rate with respect to instantaneous muscle length under all conditions. Results suggest that a longer muscle length at the time of activation leads to the development of higher loads on the contractile element during subsequent shortening, resulting in a slower shortening velocity. This plasticity of the force-velocity relationship may result from cytostructural reorganization of the smooth muscle cells in response to contractile activation at different muscle lengths.

Animals↗

Salbutamol enhances isotonic contractile properties of rat diaphragm muscle.

The effects of the beta2-adrenoceptor agonist salbutamol (Slb) on isometric and isotonic contractile properties of the rat diaphragm muscle (Diamus) were examined. A loading dose of 25 microg/kg Slb was administered intracardially before Diamus excision to ensure adequate diffusion. Studies were then performed with 0.05 microM Slb in the in vitro tissue chamber. cAMP levels were determined by radioimmunoassay. Compared with controls (Ctl), cAMP levels were elevated after Slb treatment. In Slb-treated rats, isometric twitch and maximum tetanic force were increased by approximately 40 and approximately 20%, respectively. Maximum shortening velocity increased by approximately 15% after Slb treatment, and maximum power output increased by approximately 25%. During repeated isotonic activation, the rate of fatigue was faster in the Slb-treated Diamus, but both Slb-treated and Ctl Diamus fatigued to the same maximum power output. Still, endurance time during repetitive isotonic contractions was approximately 10% shorter in the Slb-treated Diamus. These results are consistent with the hypothesis that beta-adrenoceptor stimulation by Slb enhances Diamus contractility and that these effects of Slb are likely mediated, at least in part, by elevated cAMP.

Adrenergic beta-Agonists↗

[Relaxant effects of protopine on smooth muscles].

The relaxant effects of protopine (Pro) on smooth muscles were studied by recording isotonic contraction and radioimmunoassay. Pro relaxed the contraction of rabbit thoracic aorta, mesenteric artery, portal vein and guinea pig ileum and taenia colon induced by high K+ (70 mmol.L-1). Pro also inhibited the contraction of rabbit thoracic aorta, mesenteric artery, portal vein induced by NE (0.3 mumol.L-1) and guinea pig taenia colon induced by BaCl2 (1 mmol.L-1). Pro inhibited the intracellular Ca2+ release, but did not inhibit Ca2+ influx induced by NE. These results suggested that the smooth muscle relaxant mechanism of action of Pro may be the inhibition of intracellular Ca2+ release.

Alkaloids↗

Ca2+ dependence of loaded shortening in rat skinned cardiac myocytes and skeletal muscle fibres.

This study examined the effects of activator Ca2+ on loaded shortening and power output in skinned rat cardiac myocyte preparations, and fast- and slow-twitch skeletal muscle fibres at 12 degrees C. Shortening velocities were slowed at nearly all relative loads when Ca2+ activation levels were reduced to approximately 70% maximal isometric force (P4.5) in cardiac myocyte preparations, as well as in fast-twitch and slow-twitch skeletal muscle fibres. Peak absolute power outputs declined significantly as Ca2+ activation levels were progressively reduced from maximal to 30% P4.5 in all three striated muscle types, with the greatest change in fast-twitch fibres. In cardiac myocyte preparations, even peak relative power output progressively fell when Ca2+ activation levels were lowered to approximately 70, 50 and 30% P4.5. Peak relative power output also progressively fell in fast-twitch fibres as Ca2+ activation levels were lowered from maximal down to 50% P4.5. However, in slow-twitch fibres, peak relative power output decreased only at 70% P4.5 and then remained unchanged with further reductions in Ca2+ activation levels. The greater Ca2+ dependence of peak relative power output in cardiac myocytes and fast-twitch fibres may arise from a shared mechanism such as cooperative inactivation of the thin filament, which is likely to be slowest in less cooperative slow-twitch fibres. During submaximal Ca2+ activations, the time course of shortening became markedly curvilinear during isotonic shortening in all three muscle types. The progressive slowdown in shortening velocity during isotonic contractions was greatest in fast-twitch fibres, consistent with the higher degree of cooperativity of Ca2+ activation in fast-twitch fibres. Additionally, fast-twitch and slow-twitch fibre stiffness decreased in concert with the curvature of length traces during loaded shortening. These results are consistent with the idea that cooperative inactivation of the thin filament occurs during loaded shortening and such a mechanism may contribute to the progressive slowing and overall Ca2+ dependence of loaded shortening velocity.

Animals↗

Changes in fusimotor discharge rate provoked by isotonic fatiguing muscle contractions in decerebrate cats.

Changes in discharge rate of 26 fusimotor neurones to medial gastrocnemius muscle were studied during isotonic fatiguing contractions of lateral gastrocnemius and soleus muscles in decerebrate cats. Muscle contractions were elicited by either continuous or repetitive electrical stimulation of the muscle nerves. The muscles were considered to be fatigued when, against a load equal to one third of the tension developed at the onset of an isometric contraction, i.e. to the tension indicating isometrically-induced fatigue, they returned to the length at which the isometric contraction was elicited. At the onset of muscle contraction an increase in discharge rate, lasting for 5-220 s, occurred in all except one of the neurones. In 73% of the units a late increase developed in addition in parallel with muscle fatigue outlasting the contraction for 5-180 s. All but one of the remaining neurones exhibited a short lasting burst of spike discharges coincident with the end of contraction. Enhancement of the late increase by muscle ischaemia indicates contribution of chemosensitive small-diameter muscle afferents, while the short lasting burst is supposed to be elicited rather by the mechanosensitive units sensitized by metabolic products liberated during contraction and/or fatigue. Differences of the fusimotor reflex responses to isotonic vs. isometric contraction and/or fatigue and their possible functional role are discussed.

Animals↗

Thermodynamic studies with acetylthiocholine on nicotinic receptors of mammalian skeletal muscle in vitro.

The temperature dependency of binding of acetylthiocholine, a specific nicotinic agonist, to the nicotinic receptor of mammalian skeletal muscle was studied using isotonic contractions of the rat denervated diaphragm preparation in vitro. The dissociation constants at different temperatures (22-39 degrees) were determined by the Furchgott method using alpha-bungarotoxin as an irreversible antagonist. Both free energy of association (delta G zero = -22.93 kJ/mol at 37 degrees) and enthalpy of binding (delta H zero = -58.35 kJ/mol) calculated from Kd (dissociation constant) and slope of lnKd versus 1/T (van't Hoff plot) respectively were found to be negative. The negative entropy value (delta S zero = -0.113 kJ/mol/deg) obtained from the intercept of this van't Hoff plot differs from the large positive value obtained earlier employing radioligand binding studies of the nicotinic receptor of Electrophorus electricus.

Acetylthiocholine↗

Exercise-induced neuromuscular dysfunction under reflex conditions.

The purpose of this research was to describe further the effects of exercise-induced muscle damage on reflex sensitivity. The subjects were eight physically active, but untrained males, between the ages of 18 and 29 years. The effects of eccentric and concentric exercise on patellar tendon reflex responses were determined. The 8 week experiment consisted of two, 5 day, test protocols with a 6 week wash-out period between test protocols. Each 5 day test protocol consisted of the following six test sessions: (1) day 1--baseline, (2) day 2 baseline, (3) day 2--immediate post-exercise, and (4-6) days 3-5: 24, 48, and 72 h post-exercise. On day 2, the subjects made either 100 fatiguing concentric or eccentric isotonic contractions using the right leg at 75% of the corresponding repetition maximum values. During each test session, the electromyogram (EMG) and force-time characteristics of basic and conditioned patellar tendon reflex responses were measured. The reflex amplitudes of basic and conditioned patellar tendon reflex responses were decreased following fatiguing concentric exercise. There were no immediate effects of fatiguing eccentric exercise on the basic and conditioned patellar tendon reflex responses, but the EMG amplitudes of these reflex responses were reduced on the days following eccentric exercise. The amount of conditioned patellar tendon reflex facilitation was decreased following the concentric exercise protocol and at 48 h post-eccentric exercise. Our conditioned reflex data suggest that post-exercise changes to the physiological mechanisms that modulate the recruitment gain of the alpha-motoneuron pool may depend upon the type of fatiguing exercise.

Adolescent↗

Effect of theophylline on the velocity of diaphragmatic muscle shortening.

The present study examined the effect of theophylline on the shortening velocity of submaximally activated diaphragmatic muscle (i.e., muscles were activated by the use of a level of stimulation, 50 Hz, within the range of phrenic neural firing frequencies achieved during breathing, whereas maximum activation is achieved at 300 Hz). Experiments were performed in vitro on strips of diaphragmatic muscle obtained from 21 Syrian hamsters. Muscle shortening velocity was assessed during isotonic contractions against a range of afterloads, and Hill's characteristic equation was used to calculate velocity at zero load. In addition, unloaded shortening velocity was also measured by the slack test, i.e., from the time required for muscles to take up slack after a sudden reduction in muscle length. Theophylline (160 mg/l) increased the velocity of muscle shortening against a wide range of external loads (0-14 N/cm2) and increased the extrapolated unloaded velocity of shortening from 6.4 +/- 0.9 to 7.9 +/- 1.1 (SE) lengths/s (P less than 0.01). Theophylline reduced the time required to take up slack for any given step change in muscle length, increasing the unloaded velocity of shortening assessed by the slack test from 7.6 +/- 0.9 to 9.3 +/- 1.1 lengths/s (P less than 0.002). The effect of theophylline on diaphragmatic shortening velocity was evident at concentrations as low as 40 mg/l and increased progressively as theophylline concentrations were increased to 320 mg/l. Theophylline increased the shortening velocity of fatigued as well as fresh muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of endothelin-1 on the contractility of cardiomyocytes from the spontaneously hypertensive rat.

1. Disturbances in cardiovascular responsiveness to endogenous endothelin-1 (ET-1) may play a significant role in the pathogenesis of essential hypertension. In this study the inotropic responses of cardiomyocytes derived from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rat (SHR) strains to ET-1 (10(-11)-10(-8) mol/L) were characterized. Isotonic contraction cycles of ventricular cardiomyocytes isolated from age-matched (11 week) WKY and SHR rats were recorded using a rapid digital imaging technique and evaluated by computation of a range of normalized parameters. 2. The maximum effect of ET-1, eliciting a 60-70% increase in myocyte shortening after 3 min, was observed at 10(-9) mol/L in both strains, and was associated with elevations in the rate of shortening and lengthening, abbreviated latency, contractile cycle prolongation and delayed time to peak shortening. 3. No evidence for a significant strain dependent difference in the relative responsiveness to ET-1 was detected. This finding indicates that altered sensitivity to ET-1 is unlikely to be a major factor underlying the development of hypertension in this model. 4. The distinct nature of the alterations in contractile parameters produced by ET-1 compared with angiotensin II (AII) suggests that the prevailing cellular mechanisms of action of these peptides are different and that ET-1 is not a paracrine or autocrine inotropic intermediate for AII.

Angiotensin II↗

Blood flow distribution and its temporal variability in stimulated dog gastrocnemius muscle.

The distribution of blood flow in skeletal muscle stimulated to rhythmic isotonic contractions was studied by injections of radioactive microspheres into the arterial supply in 8 gastrocnemius muscles (mean weight 84 g) of 6 anesthetized dogs (20-25 kg body weight). The distribution of 10 micron microspheres in regions of about 0.5 g was very similar to that of the standard 15 micron microspheres, whereas that of 25 micron microspheres was more uneven. The coefficient of variation (CV = SD/mean) of the ratio of simultaneously injected 10 micron and 15 micron microspheres, 0.12, was taken as the inherent scatter of the method. The average spatial distribution inequality of 10-15 micron microspheres corresponded to a CV of 0.45 and the specific local blood flow inhomogeneity to a CV = 0.43 ( = square root 0.45(2) - 0.12(2], but there were marked differences between muscles. At equal blood flow levels, the inhomogeneity during reactive hyperemia was similar to that observed during stimulation. The temporal variability of blood flow in individual muscle pieces was obtained from the comparison of fractional trapping of 4 to 5 differently labeled microspheres injected at intervals of 2 min into steadily stimulated muscles. The mean CV for the variations in time was 0.23 and that corrected for methodological scatter, 0.19, but the differences in the extent of temporal blood flow changes among muscle pieces within a muscle and between different muscles were large. The presence of considerable spatial and temporal variations of blood flow in exercising muscle during apparent steady state may be important in limiting and/or modulating tissue O2 supply.

Animals↗

Contraction kinetics of striated muscle fibres following quick changes in load.

1. The contraction kinetics of single striated muscle fibres and small fibre bundles from the frog and the toad were measured when the load was changed from P(0) to L < P(0). Simultaneous recordings were made of displacement at one end and force at the other end of the preparation.2. After the load was changed, the contractile force generally reached a steady value before the contraction velocity became steady. The amount of time required for isotonic contraction to become steady depended on the change in fractional load and on the temperature; it did not depend on sarcomere length in the range 2.2-3.0 mu or on the number of fibres in the preparation. The characteristics of the non-steady state are described in terms of the displacement deviation (the difference between the actual displacement at a given time and the back extrapolation of the steady phase of the displacement record) and the null times (the times at which the displacement deviation became zero, measured relative to the time at which the contractile force first reached the value of the load).3. The time average of the transient velocity was approximately equal to the final steady velocity.4. The product of the null time following a given relative force step and V(max), the steady velocity of unloaded contraction, was found to be independent of temperature. This is taken as evidence that the isotonic velocity transients originate in the contractile mechanism.5. The non-steady state following step changes in load is identified with the motion of cyclic contraction mechanisms. The motion of the specific model formulated by A. F. Huxley (1957) was compared with that of frog muscle fibres and, although the transients in the two systems differ in detail, the characteristic dimensions are of the same order.

Animals↗

Contractions of frog tonus fibers and their modification by length changes.

Isometric and isotonic contractions of the tonus fibers of the frog were recorded using anodal block of the nerve fibers of the twitch fibers. Repetitive stimulation produced a contraction with a very slow rising phase because the individual responses were very weak. The first two or three stimuli usually did not give a visible response at all. However, if the twitch fibers were also stimulated, the responses of the tonus fibers were many times stronger and faster, but only under isotonic conditions. This indicates that the large increase in the responses of the tonus fibers was produced by the passive shortening caused by the contraction of the twitch fibers. A strong and fast response of the tonus fibers was also obtained if during stimulation of the tonus fibers the muscle was made to shorten by diminishing the load. It is suggested that the enormous effect of shortening is due to the regenerating action of shortening previously demonstrated.

Animals↗

[Possible significance of the lipoxygenase pathway of arachidonic acid metabolism for the pathogenesis of constrictive reactions of lung blood vessels].

Recent studies suggest a key role of lipoxygenase (LOX) pathway of arachidonic acid (AA) metabolism in the regulation of pulmonary artery tone. We investigated the influence of specific inhibition of leucotriene biosynthesis on constrictory reactions of isolated rabbit pulmonary arteries in the organ bath. The substance FLM 5,011 selectively inhibiting the LOX pathway leads at a bath concentration of 5 X 10(-5) M to an inhibition in the order of 75% of AA- and phospholipase (PLP) A2-induced contraction (cumulative measurement, 37 degrees C, pH 7.4, isotonic contraction). The inhibitory effect on calciumionophore A 53,712-induced contraction was only 31.4%. We compared these findings with actions of nordihydroguiaretic acid and PAMBA. Our findings suggest that in rabbit lung arteries receptors for AA-products must exist and that the activation of AA depends on calcium. The present investigations underline the relevance of LOX products to genesis of pulmonary hypertension in man.

Arachidonic Acid↗

The force-velocity relation in phasic contractions of venous smooth muscle.

The force-velocity relation of the rat portal vein has been studied during regular spontaneous contractions induced by elevated levels of [K-+]O AND [Ca-2+]o. No satisfactory description of the force-velocity relation was obtained by measuring shortening velocity in afterloaded isotonic contractions. Therefore the method of isotonic quick release was used, as this permits mechanical studies at specified instants of the contraction-relaxation cycle. The temporal development of the force-velocity relation in the phasic response was investigated. During a time interval in the rising phase of the contraction, at about the time for maximal dP/dt, the force-velicity curves were practically identical, suggesting a plateau in the intensity of active state. At later stages of the twitch the curves were progressively displaced towards the origin, the intercepts on both the force and the velocity axis becoming smaller. At the time of the isometric peak the maximal shortening velocity had declined relatively more than the isometric force. This is presumably caused by inhomogeneous activation of the muscle at the beginning of relaxation, The maximal force-velocity relation in the rising phase of the contraction can be described by Hill's (1938) equation with the following parameters (at 37 degrees tc): a/Po = 0.73 plus or minus 0.04, b = 0.54 plus or minus 0.04 lengths/s, Vmax = 0.74 plus or minus 0.02 lengths/s (n = 7, mean plus or minus S.E,). The force-velocity relation of the portal vein in comparison with other kinds of muscle is discussed.

Animals↗

Recording and evaluation of isotonic and isometric contractions of skeletal muscle in situ.

A procedure is described for obtaining records and identifying curves of isotonic and isometric contractions (both tetanic and twitch) of the gastrocnemius muscle of the rabbit in situ. The experimental conditions have made it possible to follow the above mentioned phenomena and to measure further parameters in series at sequentially altered muscle lengths and loads acting in the course of isotonic contractions.

Animals↗

Relationships of the surface electromyogram to the force, length, velocity, and contraction rate of the cineplastic human biceps.

A series of experiments was performed to measure the relationships between the integrated surface EMG and the mechanical state of the cineplastic biceps muscle of one subject. The muscle was studied during static and dynamic isometric contractions at different muscle lengths and during constant velocity isotonic contractions at different loads. The cineplastic biceps results are compared with results obtained from the intact biceps.

Arm↗

Pharmacological studies on supersensitization. VI. Effect of cocaine on the utilization of calcium in acetylcholine-induced contraction of isolated vas deferens of guinea pig.

Effects of cocaine on the isotonic contractions of isolated intact and glycerinated vas deferens of guinea pig were examined. Cocaine potentiated the contractile responses of vas deferens to acetylcholine and potassium chloride in standard and calcium-free Tyrode solution. Cocaine also augmented the maximum response of calcium-induced contraction of partially depolarized vas deferens. The contractile responses to potassium chloride in standard Tyrode solution were completely abolished by lanthanum chloride, while the contractile responses to acetylcholine in standard Tyrode solution were attenuated by lanthanum chloride and the residual contractions were not affected by cocaine. The half-time of decrease in acetylcholine-induced contraction in calcium-free Tyrode solution was significantly different from that of potassium-induced contraction in calcium-free Tyrode solution. Cocaine did not affect the contractile response of the glycerinated muscle piece of vas deferens. These results suggest that cocaine facilitates the transmembrane influx of calcium from extracellular fluid and/or superficial calcium-binding sites without affecting the release of calcium from intracellular calcium-binding sites.

Acetylcholine↗

A probe for measurements of related values of cross-sectional area and pressure in the resting female urethra.

A probe for measurement of related values of cross sectional area (c.a.) and pressure in the resting female urethra has been developed. C.a. can be measured in the range 0.07 to 0.79 cm2 by means of the field gradient principle. Pressure is measured in the range 0 to 150 cm H2O. Pressure needed for inflation and deflation of the balloon ranges from +4 to -5 cm H2O with a hysteresis of 3 to 4 cm H2O. The probe is able to follow changes of the c.a. up to 0.7 cm2/sec. The method makes possible estimation of urethral stiffness/rigidity during distension of the balloon, estimation of the capability of contraction of the closure apparatus in terms of isometric and isotonic contraction, muscular work and power. Furthermore, hysteresis during inflation and deflation of the balloon can be described.

Calibration↗