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Sample records for rat anococcygeus muscle

  1. Enhanced noradrenergic transmission in the spontaneously hypertensive rat anococcygeus muscle

    PubMed Central

    Jiménez-Altayó, Francesc; Giraldo, Jesús; McGrath, John C; Vila, Elisabet

    2003-01-01

    There is a long-known hyper-responsiveness of vascular adrenergic transmission in the spontaneously hypertensive rat (SHR) that is uncovered specifically in the presence of cocaine and attributed to blockade of the neuronal monoamine transporter. We have now used the rat anococcygeus muscle to investigate whether this phenomenon is generic to sympathetic transmission to smooth muscle rather than a purely vascular phenomenon. We sought the origin of the effect by successively blocking the buffering effects of the neuronal monoamine transporter, prejunctional α2-adrenoceptors and NO from nitrergic nerves with desipramine (0.1 μM), rauwolscine (0.01 μM) and L-NG-nitro-arginine (100 μM). In the presence of desipramine, contractile responses to electrical field stimulation but not to noradrenaline (1 nM–100 μM) were greater in SHR than in Wistar–Kyoto (WKY). Neither inhibition of prejunctional α2-adrenoceptors nor the blockade of neuronal nitric oxide synthase (nNOS) accounted for the differential enhancement of response in SHR. The enhanced effectiveness of motor neurotransmission in SHR becomes most apparent when all known major buffering mechanisms are removed. When nitrergic responses were isolated pharmacologically (phentolamine 1 μM and guanethidine 30 μM; tone raised with carbachol 50 μM), they were not different between SHR and WKY. Western blots showed that both nNOS and tyrosine hydroxylase are expressed to a similar extent in anococcygeus muscle from SHR and WKY, suggesting similar adrenergic and nitrergic innervations in the two strains. This suggests that enhanced motor transmission is due to increased transmitter release per varicosity rather than there being normal transmission from a greater number of sites. We conclude that there is a generic enhancement of sympathetic transmission in SHR rather than this being a vascular phenomenon. PMID:14504140

  2. Effects of TRIM on tension, intracellular calcium and nitrergic transmission in the rat anococcygeus muscle.

    PubMed

    Che, Yan; Potocnik, Simon; Ellis, Anthie; Li, Chun Guang

    2007-02-01

    The effects of the putatively selective inhibitor of neuronal nitric oxide synthase (nNOS) 1-(2-trifluoromethylphenyl) imidazole (TRIM) were investigated on contractility, intracellular calcium and nitrergic relaxations in the rat anococcygeus muscle. TRIM (100-1000 microM) reduced the tension of rat anococcygeus muscles when contracted with guanethidine (10 microM) and clonidine (0.1 microM). Relaxations to TRIM persisted in the presence of the non-selective NOS inhibitor L-NAME (100 microM) and the inhibitor of soluble guanylate cyclase ODQ (1 microM). TRIM also reduced tension when muscles were contracted with phenylephrine (3 microM), noradrenaline (3 microM) or high K physiological salt solution (high KPSS; 60mM). Influx of calcium ([Ca(2+)](i)) in response to high KPSS was significantly reduced in the presence of TRIM (1mM). TRIM also inhibited the influx of (45)Ca(2+) induced by KPSS, but had no effect on the influx induced by phenylephrine (10 microM). TRIM (300 microM) had a modest, but significant, inhibitory effect on nitrergic relaxations that were evoked by electrical field stimulation (1-10 Hz, 15 V, 10s trains) in muscles contracted with guanethidine and clonidine. In contrast, L-NAME (1-100 microM) inhibited these nitrergic responses with an IC(50) of 9.31+/-0.87 microM (n=4). The results suggest that the smooth muscle relaxant effect of TRIM in the rat anococcygeus muscle may affect the entry of Ca(2+) possibly through voltage-operated calcium channels. Furthermore, the relatively modest effect of TRIM on nitrergic responses indicates that it is not a particularly reliable inhibitor of nNOS.

  3. Inhibitory action of gamma-aminobutyric acid on the excitatory but not inhibitory innervation of the rat anococcygeus muscle.

    PubMed

    Hughes, P R; Morgan, P F; Stone, T W

    1982-12-01

    1 The effects of gamma-aminobutyric acid (GABA), ethylenediamine, 3-aminopropane sulphonic acid and (+/-)-baclofen have been examined on the responses to stimulation of the adrenergic excitatory and non-adrenergic non-cholinergic inhibitory innervation of the rat anococcygeus muscle in vitro. 2 GABA produced a dose-related depression of the contractile responses to field stimulation. Ethylenediamine and baclofen also depressed the contractile responses, though they were less potent than GABA. 3-Aminopropane sulphonic acid was almost inactive. The inhibitory action of GABA was not modified by phentolamine, propranolol or bicuculline methylbromide. 3 GABA did not affect the contractile responses of the anococcygeus muscle to noradrenaline, phenylephrine or carbachol in untreated muscles or those treated with 6-hydroxydopamine in vitro. 4 In preparations in which tone was raised by continuous perfusion with carbachol in the presence of phentolamine, field stimulation relaxed the muscle. GABA had no effect on this inhibitory response, and did not itself produce any relaxation. 5 It is concluded that GABA exerts a presynaptic inhibitory action on the excitatory adrenergic but not on the inhibitory innervation of the anococcygeus muscle, and that the GABA receptor involved exhibits properties of the previously described GABAB site.

  4. 3-Aminopropylphosphinic acid--a potent, selective GABAB receptor agonist in the guinea-pig ileum and rat anococcygeus muscle.

    PubMed

    Hills, J M; Dingsdale, R A; Parsons, M E; Dolle, R E; Howson, W

    1989-08-01

    1. 3-Aminopropylphosphinic acid, a gamma-aminobutyric acid (GABA) analogue, was tested for activity on guinea-pig isolated ileum and rat isolated anococcygeus muscle preparations. The effects of 3-aminopropylphosphinic acid were compared with those of GABA and baclofen. 2. In the electrically stimulated ileum, 3-aminopropylphosphinic acid, like GABA and baclofen, caused a concentration-dependent inhibition of the cholinergic twitch contraction, the IC50 value being 1.84 +/- 0.23 microM (n = 12). Unlike GABA, but like baclofen, 3-aminopropylphosphinic acid did not produce an initial contraction. 3. The inhibitory effects of 3-aminopropylphosphinic acid and baclofen in the guinea-pig ileum were not significantly antagonized by bicuculline (10 microM), phentolamine plus propranolol (both 1 microM), yohimbine (1 microM), naloxone (1 microM), impromidine (1 microM) or 8-phenyltheophylline (10 microM). The inhibitory effects of 3-aminopropylphosphinic acid, but not of baclofen, were however antagonized by phaclofen (500 microM). In addition the effects of 3-aminopropylphosphinic acid were abolished by baclofen desensitization in the guinea-pig ileum. 4. 3-Aminopropylphosphinic acid, GABA and baclofen reduced the twitch contraction evoked by electrical field stimulation in the rat anococcygeus muscle. The IC50 for 3-aminopropylphosphinic acid inhibition of the anococcygeus contraction was 0.89 +/- 0.15 microM (n = 8). 5. It is concluded that 3-aminopropylphosphinic acid is a potent, selective GABAB agonist, being seven times more potent than baclofen in the guinea-pig ileum and five times more potent than baclofen in the rat anococcygues muscle preparations.

  5. Antispasmodic and relaxant effects of the hidroalcoholic extract of Pimpinella anisum (Apiaceae) on rat anococcygeus smooth muscle.

    PubMed

    Tirapelli, Carlos R; de Andrade, Claudia R; Cassano, Adriano O; De Souza, Fernando A; Ambrosio, Sergio R; da Costa, Fernando B; de Oliveira, Ana M

    2007-03-01

    The present work describes the mechanisms involved in the muscle relaxant effect of ethanol:water (40:60, 60:40 and 80:20) aerial parts extracts of Pimpinella anisum. Three hidroalcoholic extracts in which the proportion of ethanol was 40% (HA(40%)), 60% (HA(60%)) or 80% (HA(80%)) were tested for activity in the rat anococcygeus smooth muscle. The three extracts (50 microg/mL) inhibited acetylcholine-induced contraction. The extract HA(60%) (5-50 microg/mL) concentration dependently relaxed acetylcholine-pre-contracted tissues (31.55+/-3.56%). Conversely, HA(40%) and HA(80%) did not exert relaxant action. Pre-incubation of the preparations with N(G)-nitro-L-arginine methyl ester (L-NAME, 100 microM), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 3 microM) and oxyhemoglobin (10 microM) reduced the relaxation induced by HA(60%) (percentage of relaxation: 6.81+/-1.86%, 13.13+/-5.87% and 2.12+/-1.46%, respectively). Neither indomethacin (10 microM) nor tetraethylammonium (1 mM) affected the relaxation induced by HA(60%). Incubation of the tissues with L-NAME significantly enhanced the maximal contraction induced by acetylcholine, indicating an inhibitory role for NO in the modulation of the contractile response of anococcygeus smooth muscle to acetylcholine. However, simultaneous addition of L-NAME and HA(60%) resulted in an effect similar to that observed with L-NAME alone, further confirming the observation that Pimpinella anisum acts by realizing NO. Additionally, HA(60%) did not alter CaCl(2)-induced contraction. Collectively, our results provide functional evidence that the effects elicited by the hidroalcoholic extract of Pimpinella anisum involve the participation of NO and subsequent activation of the NO-cGMP pathway. The relaxant action displayed by Pimpinella anisum justifies its use in the folk medicine as an antispasmodic agent.

  6. The effect of ethanol on inhibitory and motor responses in the rat and rabbit anococcygeus and the bovine retractor penis muscles.

    PubMed Central

    Gillespie, J. S.; Hunter, J. C.; McKnight, A. T.

    1982-01-01

    1 Ethanol (200 mM) reduced the response to inhibitory nerve stimulation in the rat and rabbit anococcygeus and the bovine retractor penis (BRP) muscles. Ethanol also reduced the response to the inhibitory extract from the BRP consistent with the inhibitory factor in these extracts playing some part in the response to inhibitory nerve stimulation. 2 Ethanol's effect on the response to other inhibitory stimuli was examined in the rabbit anococcygeus and the BRP. In the anococcygeus the response to carbachol was reduced, to bradykinin and isobutylmethylxanthine (IBMX) unaltered, and to isoprenaline and adenosine 5'-triphosphate (ATP) potentiated. In the BRP responses to IBMX and sodium nitroprusside were unaltered but in this tissue the response to isoprenaline was reduced. Ethanol's ability to reduce inhibitory responses is, therefore, selective and confined to inhibitory nerve stimulation, inhibitory extract, carbachol, and, in the BRP, isoprenaline. 3 Ethanol reduced the rate of development of inhibition even where the magnitude of the inhibitory response was unaltered. 4 In the rat anococcygeus, ethanol (200 mM) potentiated the response to motor nerve stimulation and to noradrenaline (NA) at low frequencies and low concentrations respectively. Higher ethanol concentrations (400 mM) reduced the response to both motor nerve stimulation and NA. The motor response to carbachol was also reduced. 5 Ethanol (200 mM) itself caused an easily reversible contraction in all three tissues. This was not due to the release of NA but was highly sensitive to the removal of external calcium from the medium. 6 A unified explanation of these varied effects of ethanol based on a reduction in membrane binding of calcium and a reduced efficiency of receptor coupling is suggested. PMID:7074282

  7. A comparative study of sildenafil, NCX-911 and BAY41-2272 on the anococcygeus muscle of diabetic rats.

    PubMed

    Kalsi, Jasjit S; Ralph, David J; Madge, David J; Kell, Phil D; Cellek, Selim

    2004-12-01

    We compared the effects of a nitric oxide (NO)-releasing sildenafil (NCX-911), NO-independent soluble guanylate cyclase activator (BAY41-2272) and sildenafil on the anococcygeus muscle from streptozotocin-induced 16-weeks diabetic rats. NCX-911, BAY41-2272 and sildenafil reduced the phenylephrine-induced tone in the control group (EC50=1088.8+/-165.0, 151.6+/-9.3 and 827.1+/-167.3 nM, respectively). The potencies of NCX-911 and BAY41-2272 were not altered, but that of sildenafil was significantly reduced in the diabetic group. EC50 values for NCX-911, BAY41-2272 and sildenafil in the diabetic group were 1765.9+/-303.5, 209.7+/-27.3 and 2842.2+/-640.3 nM, respectively (P<0.05 for sildenafil). Nitrergic relaxation responses were significantly decreased in the diabetic group. The remaining nitrergic relaxation responses were potentiated by BAY41-2272 but not by sildenafil or NCX-911. These results confirm that endogenous NO derived from nitrergic nerves is significantly decreased in diabetes, and suggest that NO-releasing PDE5 inhibitors and NO-independent soluble guanylate cyclase activators could be more useful than PDE5 inhibitors in the treatment of ED in long-term diabetes.

  8. Some electrical properties of the rabbit anococcygeus muscle and a comparison of the effects of inhibitory nerve stimulation in the rat and rabbit

    PubMed Central

    Creed, Kate E.; Gillespie, J. S.

    1977-01-01

    1. Simultaneous recordings of mechanical activity and membrane potential of individual smooth muscle cells have been made in the rabbit anococcygeus muscle and the effect of field stimulation on these examined. 2. In the absence of tone the mean resting membrane potential was - 48 mV. In the stretched muscle spontaneous tone and rhythmic activity quite frequently appeared and this was associated with depolarization of the muscle cells. 3. The response to field stimulation depended on the frequency of stimulation, the level of membrane potential and the presence of myogenic tone. The usual response to single pulses or low frequency stimulation was a hyperpolarization of up to 30 mV (mean 14±6·8 mV) after a latency of 185 msec and accompanied by muscle relaxation. Higher frequencies (over 8 Hz) produced an initial depolarization often with a spike potential and followed by hyperpolarization. The mechanical response in these instances was contraction or contraction followed by relaxation. At all frequencies rebound depolarization and an associated contraction followed the end of stimulation). 4. Phentolamine (5×10-6 M) and guanethidine (10-6 M) blocked the initial depolarization and contraction but had no effect on hyperpolarization, muscle relaxation or rebound depolarization and contraction. 5. The effect of field stimulation in the presence of guanethidine (4×10-5 M) was re-examined in the rat anococcygeus. Single pulses were ineffective, repetitive stimulation produced muscle relaxation but no hyperpolarization comparable to the rabbit. Any oscillations in membrane potential were damped during field stimulation and sometimes a small hyperpolarization was produced with a maximum amplitude of 13 mV and a mean of 1·9±1·2 mV. 6. The transmembrane potential at the peak of hyperpolarization in the rabbit was rarely more than -70 mV. Passive displacement of the membrane potential by current pulses altered the amplitude of the hyperpolarization and suggested that

  9. Force and intracellular Ca2+ during cyclic nucleotide-mediated relaxation of rat anococcygeus muscle and the effects of cyclopiazonic acid.

    PubMed Central

    Raymond, G. L.; Wendt, I. R.

    1996-01-01

    1. Simultaneous recordings of tension and [Ca2+]i were made in rat anococcygeus muscle strips to investigate possible mechanisms involved during cyclic nucleotide-mediated relaxation. Relaxation of pre-contracted muscles was induced by sodium nitroprusside (SNP) or forskolin and the effects of cyclopiazonic acid (CPA) on these responses were examined. 2. In muscles pre-contracted with 0.2 microM phenylephrine addition of SNP (10 microM) caused a rapid and near complete relaxation of force. This was accompanied by a decrease in [Ca2+]i, however, this was not of a comparable magnitude to the decrease in force. The level of [Ca2+]i in muscles relaxed with SNP was shown to be associated with substantially higher force levels in the absence of SNP. Forskolin (10 microM) caused a slower, essentially complete relaxation which was associated with a proportional decrease in [Ca2+]i. 3. In muscles pretreated with SNP or forskolin subsequent responses to phenylephrine were attenuated with both force and [Ca2+]i rising slowly to attain eventually levels similar to those observed when the relaxant was applied to pre-contracted muscles. 4. Exposure of the muscles to the sarcoplasmic reticulum Ca(2+)-ATPase inhibitor, CPA (10 microM), resulted in a sustained increase in [Ca2+]i which, in most cases, was not associated with any force development. The relaxation and decrease in [Ca2+]i in response to both SNP and forskolin were attenuated and substantially slowed in the presence of CPA. Overall the extent of this attenuation was greater for SNP. For both SNP and forskolin, CPA attenuated the decrease in [Ca2+]i to a greater extent than the decrease in force. In some cases, SNP-mediated relaxation in the presence of CPA was observed with almost no detectable change in [Ca2+]i. 5. The results suggest that, in the rat anococcygeus muscle under normal circumstances, a lowering of [Ca2+]i can fully account for the relaxation induced by forskolin but not for that induced by SNP, where

  10. Cellular mechanisms underlying carbachol-induced oscillations of calcium-dependent membrane current in smooth muscle cells from mouse anococcygeus

    PubMed Central

    Wayman, Christopher P; McFadzean, Ian; Gibson, Alan; Tucker, John F

    1997-01-01

    At a holding potential of −40 mV, carbachol (50 μM) produced a complex pattern of inward currents in single smooth muscle cells freshly isolated from the mouse anococcygeus. Membrane currents were monitored by the whole-cell configuration of the patch-clamp technique. Previous work has identified the first, transient component as a calcium-activated chloride current (ICl(Ca)) and the second sustained component as a store depletion-operated non-selective cation current (IDOC). The object of the present study was to examine the cellular mechanisms underlying the third component, a series of inward current oscillations (Ioscil) superimposed on IDOC.Carbachol-induced Ioscil (amplitude 97±11 pA; frequency 0.26±0.02 Hz) was inhibited by the chloride channel blocker anthracene-9-carboxylic acid (A-9-C; 1 mM), and by inclusion of 1 mM EGTA in the patch-pipette filling solution.In calcium-free extracellular medium (plus 1 mM EGTA), carbachol produced an initial burst of oscillatory current which lasted 94 s before decaying to zero; Ioscil could be restored by re-admission of calcium. The frequency, but not the amplitude, of Ioscil increased with increasing concentrations of extracellular calcium (0.5–10 mM).Inclusion of the inositol triphosphate (IP3) receptor antagonist heparin (5 mg ml−1) in the patch-pipette filling solution, or pretreatment of cells with the sarcoplasmic reticulum (SR) calcium ATPase inhibitor cyclopiazonic acid (CPA; 10 μM), prevented the activation of Ioscil by carbachol. Caffeine (10 mM) activated both ICl(Ca) and IDOC and prevented the induction of Ioscil by carbachol. Caffeine and CPA also abolished Ioscil in the presence of carbachol, as did both a low (3 μM) and a high (30 μM) concentration of ryanodine.Carbachol-induced Ioscil was abolished by the general calcium entry blocker SKF 96365 (10 μM) and by Cd2+ (100 μM), but was unaffected by La3+ (400 μM). As found previously, IDOC was also blocked by

  11. Structural limits on force production and shortening of smooth muscle.

    PubMed

    Siegman, Marion J; Davidheiser, Sandra; Mooers, Susan U; Butler, Thomas M

    2013-02-01

    This study determined the factors that limit force production and shortening in two smooth muscles having very different relationships between active and passive force as a function of muscle length. The rat anococcygeus muscle develops active force over the range of lengths 0.2-2.0× the optimum length for force production (Lo). Passive tension due to extension of the resting muscle occurs only at lengths exceeding Lo. In contrast, the rabbit taenia coli develops force in the range of lengths 0.4-1.1 Lo, and passive force which is detectable at 0.56 Lo, increases to ~0.45 maximum active force at Lo, and increases sharply with further extension. The anococcygeus muscle can shorten to 0.2 Lo and the taenia coli to 0.4 Lo. Dynamic stiffness and energy usage at short muscle lengths suggest that the limit of shortening in the taenia coli, in contrast to the anococcygeus muscle, is not due to a failure of cross bridge interaction. Phosphorylation of the regulatory myosin light chains in intact muscles decreased to a small extent at short lengths compared to the decrease in force production. The differences in force production and the extent of shortening in the two muscles was maintained even when, following permeabilization, the myosin light chains were irreversibly phosphorylated with ATPγS, indicating that differences in activation played little, if any role. Ultrastructural studies on resting and activated muscles show that the taenia coli, which is rich in connective tissue (unlike the anococcygeus muscle) undergoes marked cellular twisting and contractile filament misalignment at short lengths with compression of the extracellular matrix. As a result, force is not transmitted in the longitudinal axis of the muscle, but is dissipated against an internal load provided by the compressed extracellular matrix. These observations on two very different normal smooth muscles reveal how differences in the relative contribution of active and passive structural elements

  12. Composition of Muscle Fiber Types in Rat Rotator Cuff Muscles.

    PubMed

    Rui, Yongjun; Pan, Feng; Mi, Jingyi

    2016-10-01

    The rat is a suitable model to study human rotator cuff pathology owing to the similarities in morphological anatomy structure. However, few studies have reported the composition muscle fiber types of rotator cuff muscles in the rat. In this study, the myosin heavy chain (MyHC) isoforms were stained by immunofluorescence to show the muscle fiber types composition and distribution in rotator cuff muscles of the rat. It was found that rotator cuff muscles in the rat were of mixed fiber type composition. The majority of rotator cuff fibers labeled positively for MyHCII. Moreover, the rat rotator cuff muscles contained hybrid fibers. So, compared with human rotator cuff muscles composed partly of slow-twitch fibers, the majority of fast-twitch fibers in rat rotator cuff muscles should be considered when the rat model study focus on the pathological process of rotator cuff muscles after injury. Gaining greater insight into muscle fiber types in rotator cuff muscles of the rat may contribute to elucidate the mechanism of pathological change in rotator cuff muscles-related diseases. Anat Rec, 299:1397-1401, 2016. © 2016 Wiley Periodicals, Inc.

  13. Skeletal muscle metabolism in hypokinetic rats

    NASA Technical Reports Server (NTRS)

    Tischler, M. E.

    1984-01-01

    Muscle growth, protein metabolism, and amino acid metabolism were studied in various groups of rats. Certain groups were adrenaliectomized; some rats were suspended while others (the controls) were weight bearing. Results show that: (1) metabolic changes in the extensor digitorum longus muscle of suspended rats are due primarily to increased circulating glucocorticoids; (2) metabolic changes in the soleus muscle due to higher steroid levels are probably potentiated by greater numbers of steroid receptors; and (3) not all metabolic responses of the soleus muscle to unloading are due to the elevated levels of glucocorticoids or the increased sensitivity of this muscle to these hormones.

  14. Influence of spaceflight on rat skeletal muscle

    NASA Technical Reports Server (NTRS)

    Martin, Thomas P.; Edgerton, V. Reggie; Grindeland, Richard E.

    1988-01-01

    The effect of a 7-day spaceflight (aboard NASA's SL-3) on the size and the metabolism of single fibers from several rat muscles was investigated along with the specificity of these responses as related to the muscle type and the size of fibers. It was found that the loss of mass after flight was varied from 36 percent in the soleus to 15 percent in the extensor digitorum longus. Results of histochemical analyses showed that the succinate dehydrogenase (SDH) activity in muscles of flight-exposed rats was maintained at the control levels, whereas the alpha-glycerol phosphate dehydrogenase (GPD) activity was either maintained or increased. The analyses of the metabolic profiles of ATPase, SDH, and GPD indicated that, in some muscles, there was an increase in the poportion of fast oxidative-glycolytic fibers.

  15. Chronic Paraspinal Muscle Injury Model in Rat

    PubMed Central

    Cho, Tack Geun; Kim, Young Baeg

    2016-01-01

    Objective The objective of this study is to establish an animal model of chronic paraspinal muscle injury in rat. Methods Fifty four Sprague-Dawley male rats were divided into experimental group (n=30), sham (n=15), and normal group (n=9). Incision was done from T7 to L2 and paraspinal muscles were detached from spine and tied at each level. The paraspinal muscles were exposed and untied at 2 weeks after surgery. Sham operation was done by paraspinal muscles dissection at the same levels and wound closure was done without tying. Kyphotic index and thoracolumbar Cobb's angle were measured at preoperative, 2, 4, 8, and 12 weeks after the first surgery for all groups. The rats were sacrificed at 4, 8, and 12 weeks after the first surgery, and performed histological examinations. Results At 4 weeks after surgery, the kyphotic index decreased, but, Cobb's angle increased significantly in the experimental group (p<0.05), and then that were maintained until the end of the experiment. However, there were no significant differences of the kyphotic index and Cobb's angle between sham and normal groups. In histological examinations, necrosis and fibrosis were observed definitely and persisted until 12 weeks after surgery. There were also presences of regenerated muscle cells which nucleus is at the center of cytoplasm, centronucleated myofibers. Conclusion Our chronic injury model of paraspinal muscles in rats shows necrosis and fibrosis in the muscles for 12 weeks after surgery, which might be useful to study the pathophysiology of the degenerative thoracolumbar kyphosis or degeneration of paraspinal muscles. PMID:27651859

  16. THE HISTOGENESIS OF RAT INTERCOSTAL MUSCLE

    PubMed Central

    Kelly, A. M.; Zacks, S. I.

    1969-01-01

    Intercostal muscle from fetal and newborn rats was examined with the electron microscope. At 16 days' gestation, the developing muscle was composed of primary generations of myotubes, many of which were clustered together in groups. Within these groups, the membranes of neighboring myotubes were interconnected by specialized junctions, including tight junctions. Morphologically undifferentiated cells surrounded the muscle groups, frequently extended pseudopodia along the interspace between adjacent myotubes, and appeared to separate neighboring myotubes from one another. At 18 and 20 days' gestation, the muscle was also composed of groups of cells but the structure of the groups differed from that of the groups observed at 16 days. Single, well differentiated myotubes containing much central glycogen and peripheral myofibrils dominated each group. These large cells were interpreted as primary myotubes. Small, less differentiated muscle cells and undifferentiated cells clustered around their walls. Each cluster was ensheated by a basal lamina. The small cells were interpreted as primordia of new generations of muscle cells which differentiated by appositional growth along the walls of the large primary myotubes. All generations of rat intercostal muscle cells matured to myofibers between 20 days' gestation and birth. Coincidentally, large and small myofibers diverged from each other, leading to disintegration of the groups of muscle cells. Undifferentiated cells frequently occurred in the interspaces between neighboring muscle cells at the time of separation. Myofibers arising at different stages of muscle histogenesis intermingled in a checkerboard fashion as a result of this asynchronous mode of development. The possibility of fusion between neighboring muscle cells in this developing system is discussed. PMID:5786979

  17. Effects of microgravity on rat muscle

    NASA Technical Reports Server (NTRS)

    Riley, D. A.

    1990-01-01

    It is well known that humans exposed to long term spaceflight experience undesirable progressive muscle weakness and increased fatigability. This problem has prompted the implementation of inflight exercise programs because most investigators believe that the major cause of diminished muscle performance is a combination of disuse and decreased workload. Inflight exercise has improved muscle health, but deficits have persisted, indicating that either the regimens utilized were suboptimal or there existed additional debilitating factors which were not remedied by exercise. Clarification of this question requires an improved understanding of the cellular and molecular basis of spaceflight-induced muscle deterioration. To this end, multiple investigations have been performed on the muscles from rats orbited 5 to 22 days in Cosmos biosatellites and Spacelab-3 (2,4,5,8,10 to 14,16,18,19,21 to 23,25,27,28). The eight Cosmos 1887 investigations examined the structural and biochemical changes in skeletal and cardiac muscles of rats exposed to microgravity for 12.5 days and returned to terrestrial gravity 2.3 days before tissues were collected. Even though interpretation of these results was complicated by the combination of inflight and postflight induced alterations, the consensus is that there is marked heterogeneity in both degree and type of responses from the whole muscle level down to the molecular level. Collectively, the muscle investigations of Cosmos 1887 clearly illustrate the wide diversity of muscle tissue responses to spaceflight. Judging from the summary report of this mission, heterogeneity of responses is not unique to muscle tissue. Elucidating the mechanism underlying this heterogeneity holds the key to explaining adaptation of the organism to prolonged spaceflight.

  18. Insulin binding to individual rat skeletal muscles

    SciTech Connect

    Koerker, D.J.; Sweet, I.R.; Baskin, D.G. )

    1990-10-01

    Studies of insulin binding to skeletal muscle, performed using sarcolemmal membrane preparations or whole muscle incubations of mixed muscle or typical red (soleus, psoas) or white (extensor digitorum longus (EDL), gastrocnemius) muscle, have suggested that red muscle binds more insulin than white muscle. We have evaluated this hypothesis using cryostat sections of unfixed tissue to measure insulin binding in a broad range of skeletal muscles; many were of similar fiber-type profiles. Insulin binding per square millimeter of skeletal muscle slice was measured by autoradiography and computer-assisted densitometry. We found a 4.5-fold range in specific insulin tracer binding, with heart and predominantly slow-twitch oxidative muscles (SO) at the high end and the predominantly fast-twitch glycolytic (FG) muscles at the low end of the range. This pattern reflects insulin sensitivity. Evaluation of displacement curves for insulin binding yielded linear Scatchard plots. The dissociation constants varied over a ninefold range (0.26-2.06 nM). Binding capacity varied from 12.2 to 82.7 fmol/mm2. Neither binding parameter was correlated with fiber type or insulin sensitivity; e.g., among three muscles of similar fiber-type profile, the EDL had high numbers of low-affinity binding sites, whereas the quadriceps had low numbers of high-affinity sites. In summary, considerable heterogeneity in insulin binding was found among hindlimb muscles of the rat, which can be attributed to heterogeneity in binding affinities and the numbers of binding sites. It can be concluded that a given fiber type is not uniquely associated with a set of insulin binding parameters that result in high or low binding.

  19. Distribution of slow muscle fiber of muscle spindle in postnatal rat masseter muscle.

    PubMed

    Sato, Iwao; Imura, Kosuke; Miwa, Yoko; Ide, Yoshiaki; Murata, Megumi; Sunohara, Masataka

    2007-11-01

    We investigated the properties of the muscle spindle in the masseter muscle at an immunohistochemical level in rats fed for 6 weeks. Slow myosin heavy chain (MyHC) isoforms were measured and intrafusal fibers in the muscle spindle were studied to determine the relationship between the superficial and deep regions of rat masseter muscle after alternated feeding pattern. However, muscle spindles were found in both regions, mainly in the deep region of the posterior superficial region of masseter muscle. The total number of the slow fiber in the intrafusal fiber and number of muscle spindle in the deep region were high from 5 to 8 weeks old in spite of various dimensions of data such as diameter and the compositions of the intrafusal fiber. The relationship of the protein expression of slow MyHC in the two regions at 5 weeks old reversed five weeks later (10 weeks old). This period is an important stage because the mastication system in masseter muscle with muscle spindle may be changed during the alternated feeding pattern of suckling to mastication. The changes may be a marker of the feeding system and of the control by the tension receptor of muscle spindle in this stage of masseter muscle after postnatal development.

  20. Cardiac Muscle Studies with Rat Ventricular Strips

    ERIC Educational Resources Information Center

    Whitten, Bert K.; Faleschini, Richard J.

    1977-01-01

    Details undergraduate physiology laboratory experiments that demonstrate mechanical properties of cardiac muscle, using strips from the ventricle of a rat heart. Includes procedures for obtaining length-tension curves, demonstrating the role of calcium in excitation-contraction coupling, and showing effects of several cardiovascular drugs…

  1. Segmental fibre type composition of the rat iliopsoas muscle.

    PubMed

    Vlahovic, Hrvoje; Bazdaric, Ksenija; Marijancic, Verner; Soic-Vranic, Tamara; Malnar, Daniela; Arbanas, Juraj

    2017-01-18

    The iliopsoas of the rat is composed of two muscles - the psoas major muscle and the iliacus muscle. The psoas major muscle arises from all the lumbar vertebrae and the iliacus muscle from the fifth and sixth lumbar vertebrae and ilium. Their common insertion point is the lesser trochanter of the femur, and their common action is the lateral rotation of the femur and flexion of the hip joint. Unlike humans, the rat is a quadruped and only occasionally rises up on its hind legs. Therefore, it is expected that the fibre type composition of the rat iliopsoas muscle will be different than that of humans. The iliopsoas muscle of the rat is generally considered to be a fast muscle. However, previous studies of the fibre type composition of the rat psoas muscle showed different results. Moreover, very little is known about the composition of the rat iliacus muscle. The aim of our study was to examine the fibre type composition of the rat iliopsoas muscle in order to better understand the complex function of the listed muscle. The psoas major muscle was examined segmentally at four different levels of its origin. Type I, IIA, IIB and IIX muscle fibres were typed using monoclonal antibodies for myosin heavy chain identification. The percentage of muscle fibre types and muscle fibre cross-sectional areas were calculated. In our study we showed that in the rat iliopsoas muscle both the iliacus and the psoas major muscles had a predominance of fast muscle fibre types, with the highest percentage of the fastest IIB muscle fibres. Also, the IIB muscle fibres showed the largest cross-sectional area (CSA) in both muscles. As well, the psoas major muscle showed segmental differences of fibre type composition. Our results showed changes in percentages, as well as the CSAs of muscle fibre types in cranio-caudal direction. The most significant changes were visible in type IIB muscle fibres, where there was a decrease of percentages and the CSAs from the cranial towards the caudal part

  2. Testosterone and muscle hypertrophy in female rats

    NASA Technical Reports Server (NTRS)

    Kuhn, F. E.; Max, S. R.

    1985-01-01

    The effects of chronic treatment with testosterone propionate (TP) on compensatory muscle hypertropy in female rats are examined. The 48 female rats were placed in one of four test groups: (1) no overload (synergist removal), no TP, (2) overload, no TP, (3) no overload + TP, and (4) overload + TP. The technique used to administer the TP is described. The preparation of the plantaris muscle, the analysis of pyruvate oxidation and the determination of malate and lactate dehydrogenases and the noncollogen protein are explained. The results which reveal the effect of overload and TP on body weight, noncollogen protein concentration, lactate and malate dehydrogenase activities, and pyruvate oxidation are presented and discussed. It is concluded that in terms of body weight, protein content, pyruvate, glycolysis, and oxidative metabolisms chronic TP treatments do not change compensatory muscle hypertropy.

  3. Microdialysis of triamcinolone acetonide in rat muscle.

    PubMed

    Rojas, Cioli; Nagaraja, Nelamangala V; Webb, Alistair I; Derendorf, Hartmut

    2003-02-01

    The objective of this study was to compare plasma and muscle concentrations of triamcinolone acetonide (TA) in the rat by microdialysis. Microdialysis experiments were carried out at steady state in rats after an initial I.V. bolus 50 mg/kg of the phosphate ester of TA (TAP) followed by 23 mg/kg/h infusion. In vivo recovery was calculated by retrodialysis. The concentration determined at steady state in microdialysate, corrected for recovery, was 2.73 +/- 0.42 microg/mL compared to 21.9 +/- 2.3 microg/mL in plasma. The pharmacokinetics of TA in plasma was described by an open two-compartment model with a terminal half-life of 2.7 h. The clearance of TA in rats determined by compartmental analysis was 0.94 L/h/kg. The measured microdialysate levels of TA in muscle, corrected for recovery, were comparable to the predicted free drug levels in the peripheral compartment. Protein binding in rat plasma, measured by ultrafiltration, was 90.1%. The microdialysis in vivo recovery in muscle was similar to the in vitro recovery under stirred conditions. The results show the applicability of microdialysis to measure free tissue concentrations of TA in rats.

  4. Muscle fibre types in the suprahyoid muscles of the rat

    PubMed Central

    COBOS, A. R.; SEGADE, L. A. G.; FUENTES, I.

    2001-01-01

    Five muscle fibre types (I, IIc, IIa, IIx and IIb) were found in the suprahyoid muscles (mylohyoid, geniohyoid, and the anterior and posterior bellies of the digastric) of the rat using immuno and enzyme histochemical techniques. More than 90% of fibres in the muscles examined were fast contracting fibres (types IIa, IIx and IIb). The geniohyoid and the anterior belly of the digastric had the greatest number of IIb fibres, whilst the mylohyoid was almost exclusively formed by aerobic fibres. The posterior belly of the digastric contained a greater percentage of aerobic fibres (83.4%) than the anterior belly (67.8%). With the exception of the geniohyoid, the percentage of type I and IIc fibres, which have slow myosin heavy chain (MHCβ), was relatively high and greater than has been previously reported in the jaw-closing muscles of the rat, such as the superficial masseter. The geniohyoid and mylohyoid exhibited a mosaic fibre type distribution, without any apparent regionalisation, although in the later MHCβ-containing fibres (types I and IIc) were primarily located in the rostral 2/3 region. In contrast, the anterior and posterior bellies of the digastric revealed a clear regionalisation. In the anterior belly of the digastric 2 regions were observed: both a central region, which was almost exclusively formed by aerobic fibres and where all of the type I and IIc fibres were located, and a peripheral region, where type IIb fibres predominated. The posterior belly of the digastric showed a deep aerobic region which was greater in size and where type I and IIc fibres were confined, and a superficial region, where primarily type IIx and IIb fibres were observed. PMID:11322721

  5. Muscle fiber types composition and type identified endplate morphology of forepaw intrinsic muscles in the rat.

    PubMed

    Pan, Feng; Mi, Jing-Yi; Zhang, Yan; Pan, Xiao-Yun; Rui, Yong-Jun

    2016-06-01

    The failure to accept reinnervation is considered to be one of the reasons for the poor motor functional recovery of intrinsic hand muscles (IHMs) after nerve injury. Rat could be a suitable model to be used in simulating motor function recovery of the IHMs after nerve injury as to the similarities in function and anatomy of the muscles between human and rat. However, few studies have reported the muscle fiber types composition and endplate morphologic characteristics of intrinsic forepaw muscles (IFMs) in the rat. In this study, the myosin heavy chain isoforms and acetylcholine receptors were stained by immunofluorescence to show the muscle fiber types composition and endplates on type-identified fibers of the lumbrical muscles (LMs), interosseus muscles (IMs), abductor digiti minimi (AM) and flexor pollicis brevis (FM) in rat forepaw. The majority of IFMs fibers were labeled positively for fast-switch fiber. However, the IMs were composed of only slow-switch fiber. With the exception of the IMs, the other IFMs had a part of hybrid fibers. Two-dimensional morphological characteristics of endplates on I and IIa muscle fiber had no significant differences among the IFMs. The LMs is the most suitable IFMs of rat to stimulate reinnervation of the IHMs after nerve injury. Gaining greater insight into the muscle fiber types composition and endplate morphology in the IFMs of rat may help understand the pathological and functional changes of IFMs in rat model stimulating reinnervation of IHMs after peripheral nerve injury.

  6. Age-related changes in rat intrinsic laryngeal muscles: analysis of muscle fibers, muscle fiber proteins, and subneural apparatuses.

    PubMed

    Nishida, Naoya; Taguchi, Aki; Motoyoshi, Kazumi; Hyodo, Masamitsu; Gyo, Kiyofumi; Desaki, Junzo

    2013-03-01

    We compared age-related changes in the intrinsic laryngeal muscles of aged and young adult rats by determining the number and diameter of muscle fibers, contractile muscle protein (myosin heavy chain isoforms, MHC) composition, and the morphology of the subneural apparatuses. In aged rats, both the numbers and the diameters of muscle fibers decreased in the cricothyroid (CT) muscle. The number of fibers, but not diameter, decreased in the thyroarytenoid (TA) muscle. In the posterior cricoarytenoid (PCA) muscle, neither the number nor the diameter of fibers changed significantly. Aging was associated with a decrease in type IIB and an increase in type IIA MHC isoform levels in CT muscle, but no such changes were observed in the TA or PCA muscles. Morphological examination of primary synaptic clefts of the subneural apparatus revealed that aging resulted in decreased labyrinthine and increased depression types in only the CT muscle. In the aged group, morphologically immature subneural apparatuses were found infrequently in the CT muscle, indicating continued tissue remodeling. We suggest, therefore, that age-related changes in the intrinsic laryngeal muscles primarily involve the CT muscle, whereas the structures of the TA and PCA muscles may better resist aging processes and therefore are less vulnerable to functional impairment. This may reflect differences in their roles; the CT muscle controls the tone of the vocal folds, while the TA and PCA muscles play an essential role in vital activities such as respiration and swallowing.

  7. Distraction of skeletal muscle: evolution of a rat model.

    PubMed

    Green, Stuart A; Horton, Eric; Baker, Michael; Utkan, Ali; Caiozzo, Vincent

    2002-10-01

    To better study the effects of limb lengthening on skeletal muscle, the authors developed a rat model that uses a miniature external skeletal fixator applied to the tibia of an adult Sprague-Dawley rat. The mounting and lengthening protocols follow the principles developed by Ilizarov. With the initial version of the fixator, the rats had progressive equinus contractures develop because the calf muscles resisted elongation. By incorporating a footplate in the distraction apparatus, tibial lengthening can be achieved without concomitant equinus.

  8. Mangiferin protects against adverse skeletal muscle changes and enhances muscle oxidative capacity in obese rats

    PubMed Central

    Acevedo, Luz M.; Raya, Ana I.; Martínez-Moreno, Julio M.

    2017-01-01

    Obesity-related skeletal muscle changes include muscle atrophy, slow-to-fast fiber-type transformation, and impaired mitochondrial oxidative capacity. These changes relate with increased risk of insulin resistance. Mangiferin, the major component of the plant Mangifera indica, is a well-known anti-inflammatory, anti-diabetic, and antihyperlipidemic agent. This study tested the hypothesis that mangiferin treatment counteracts obesity-induced fiber atrophy and slow-to-fast fiber transition, and favors an oxidative phenotype in skeletal muscle of obese rats. Obese Zucker rats were fed gelatin pellets with (15 mg/kg BW/day) or without (placebo group) mangiferin for 8 weeks. Lean Zucker rats received the same gelatin pellets without mangiferin and served as non-obese and non-diabetic controls. Lesser diameter, fiber composition, and histochemical succinic dehydrogenase activity (an oxidative marker) of myosin-based fiber-types were assessed in soleus and tibialis cranialis muscles. A multivariate discriminant analysis encompassing all fiber-type features indicated that obese rats treated with mangiferin displayed skeletal muscle phenotypes significantly different compared with both lean and obese control rats. Mangiferin significantly decreased inflammatory cytokines, preserved skeletal muscle mass, fiber cross-sectional size, and fiber-type composition, and enhanced muscle fiber oxidative capacity. These data demonstrate that mangiferin attenuated adverse skeletal muscle changes in obese rats. PMID:28253314

  9. Skeletal muscle metabolism in hypokinetic rats

    NASA Technical Reports Server (NTRS)

    Tischler, Marc E.

    1993-01-01

    This grant focused on the mechanisms of metabolic changes associated with unweighting atrophy and reduced growth of hind limb muscles of juvenile rats. Metabolic studies included a number of different areas. Amino acid metabolic studies placed particular emphasis on glutamine and branched-chain amino acid metabolism. These studies were an outgrowth of understanding stress effects and the role of glucocorticoids in these animals. Investigations on protein metabolism were largely concerned with selective loss of myofibrillar proteins and the role of muscle proteolysis. These investigations lead to finding important differences from denervation and atrophy and to define the roles of cytosolic versus lysosomal proteolysis in these atrophy models. A major outgrowth of these studies was demonstrating an ability to prevent atrophy of the unweighted muscle for at least 24 hours. A large amount of work concentrated on carbohydrate metabolism and its regulation by insulin and catecholamines. Measurements focused on glucose transport, glycogen metabolism, and glucose oxidation. The grant was used to develop an important new in situ approach for studying protein metabolism, glucose transport, and hormonal effects which involves intramuscular injection of various agents for up to 24 hours. Another important consequence of this project was the development and flight of Physiological-Anatomical Rodent Experiment-1 (PARE-1), which was launched aboard Space Shuttle Discovery in September 1991. Detailed descriptions of these studies can be found in the 30 peer-reviewed publications, 15 non-reviewed publications, 4 reviews and 33 abstracts (total 82 publications) which were or are scheduled to be published as a result of this project. A listing of these publications grouped by area (i.e. amino acid metabolism, protein metabolism, carbohydrate metabolism, and space flight studies) are included.

  10. Myofascial force transmission between transferred rat flexor carpi ulnaris muscle and former synergistic palmaris longus muscle

    PubMed Central

    Maas, Huub; Huijing, Peter A.

    2011-01-01

    Summary We investigated the extent of mechanical interaction between rat flexor carpi ulnaris (FCU) and palmaris longus (PL) muscles following transfer of FCU to the distal tendons of extensor carpi radialis brevis and longus (ECRB/L) muscles. Five weeks after recovery from surgery, isometric forces exerted at the distal tendons of FCU and PL were quantified at various FCU lengths. PL was kept at a constant length. Changing the muscle-tendon complex length of transferred FCU (by maximally 3.5 mm) decreased PL force significantly (by 7%). A linear relationship was found between changes in FCU muscle belly length, being a measure of muscle relative positions, and PL force. These results indicate that despite transfer of FCU muscle to the extensor side of the forearm, changing FCU length still affects force transmission of its, now, antagonistic PL muscle. We conclude that a transferred muscle may still be mechanically linked to its former synergistic muscles. PMID:23738260

  11. Tongue muscle plasticity following hypoglossal nerve stimulation in aged rats

    PubMed Central

    Connor, Nadine P.; Russell, John A.; Jackson, Michelle A.; Kletzien, Heidi; Wang, Hao; Schaser, Allison J.; Leverson, Glen E.; Zealear, David L.

    2012-01-01

    Introduction Age-related decreases in tongue muscle mass and strength have been reported. It may be possible to prevent age-related tongue muscle changes using neuromuscular electrical stimulation (NMES). Our hypothesis was that alterations in muscle contractile properties and myosin heavy chain composition would be found following NMES. Methods Fifty-four young, middle-aged and old Fischer 344/Brown Norway rats were included. Twenty-four rats underwent bilateral electrical stimulation of the hypoglossal nerves for 8 weeks and were compared with control or sham rats. Muscle contractile properties and myosin heavy chain (MHC) in the genioglossus (GG), styloglossus (SG) and hyoglossus (HG) muscles were examined. Results In comparison with unstimulated control rats, we found reduced muscle fatigue, increased contraction and half decay times and increased twitch and tetanic tension. Increased Type I MHC was found, except for GG in old and middle-aged rats. Discussion Transitions in tongue muscle contractile properties and phenotype were found following NMES. PMID:23169566

  12. Leucine supplementation improves regeneration of skeletal muscles from old rats.

    PubMed

    Pereira, Marcelo G; Silva, Meiricris T; da Cunha, Fernanda M; Moriscot, Anselmo S; Aoki, Marcelo S; Miyabara, Elen H

    2015-12-01

    The decreased regenerative capacity of old skeletal muscles involves disrupted turnover of proteins. This study investigated whether leucine supplementation in old rats could improve muscle regenerative capacity. Young and old male Wistar rats were supplemented with leucine; then, the muscles were cryolesioned and examined after 3 and 10 days. Leucine supplementation attenuated the decrease in the expression of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) and eukaryotic translation initiation factor 4E (eIF4E) in young and old muscles on day 3 post-injury and promoted an increase in the cross-sectional area of regenerating myofibers from both young and old soleus muscles on day 10 post-injury. This supplementation decreased the levels of ubiquitinated proteins and increased the proteasome activity in young regenerating muscles, but the opposite effect was observed in old regenerating muscles. Moreover, leucine decreased the inflammation area and induced an increase in the number of proliferating satellite cells in both young and old muscles. Our results suggest that leucine supplementation improves the regeneration of skeletal muscles from old rats, through the preservation of certain biological responses upon leucine supplementation. Such responses comprise the decrease in the inflammation area, increase in the number of proliferating satellite cells and size of regenerating myofibers, combined with the modulation of components of the phosphoinositide 3-kinase/Akt-protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway and ubiquitin-proteasome system.

  13. Myosin heavy chain expression in respiratory muscles of the rat.

    PubMed

    LaFramboise, W A; Watchko, J F; Brozanski, B S; Daood, M J; Guthrie, R D

    1992-03-01

    Myosin heavy chain (MHC) isoforms of hind limb adult rat muscles and muscles with a range of respiratory activities were analyzed by a sodium dodecyl sulfate polyacrylamide gel electrophoresis technique that allowed electrophoretic separation of the three fast and one slow MHC isoform found in typical rat muscle. Costal and crural diaphragm muscle samples expressed a mixture of MHC beta/slow, MHC2A, and MHC2X but little MHC2B. In contrast, MHC2B was the dominant MHC isoform in the genioglossus, intercostal, and three abdominal muscles, all of which exhibited minimal expression of MHC beta/slow. The amount of MHC2X (relative to total MHC composition) was similar in the diaphragm, genioglossus, and transversus abdominis muscles, while considerably less was detected in the rectus abdominis and external oblique muscles. These results indicate that MHC2X is broadly and variably distributed among respiratory muscles. Furthermore, these data suggest that a large portion of 2X fibers (containing MHC2X), which cannot be detected by standard histochemical analysis, may be present in the genioglossus and transversus abdominis muscles as has been demonstrated for the diaphragm muscle. We speculate that an association exists between the level of MHC2X expression and frequency of respiratory recruitment.

  14. [Electrophysiological characteristics of the isolated muscle spindle in rats].

    PubMed

    Zhao, Xue-Hong; Fan, Xiao-Li; Song, Xin-Ai; Shi, Lei

    2011-06-25

    The aim of this study was to observe the electrophysiological characteristics of the isolated rat muscle spindle. The muscle spindle was isolated from rat soleus and the afferent discharge of the isolated muscle spindle was recorded by air-gap technique. In the basic physiological salt solution, the spontaneous impulses of muscle spindle were at a lower level with irregular intervals. The mean frequency of afferents was (51.78 ± 25.63) impulses/1 000 s (n = 13). The muscle spindle afferents were significantly increased and maintained over time by the addition of certain amino acids during the observation. The number of the action potential recorded per 1 000 s was 200-1 000 [mean: (687.62 ± 312.56) impulses/1 000 s, n = 17]. In addition to the typical propagated action potential, a large number of abortive spikes were observed. The results indicate that the activities of isolated muscle spindles in rats can be well maintained by the addition of certain amino acids. The results initially establish and provide the possibility for further research conducted in isolated rat muscle spindles.

  15. Atrophy of rat skeletal muscles in simulated weightlessness

    NASA Technical Reports Server (NTRS)

    Feller, D. D.; Ginoza, H. S.; Morey, E. R.

    1982-01-01

    A hypokinetic rat model was used for elucidation of the mechanism of skeletal muscle wasting which occurs in weightlessness. Rats were suspended from a back-harness with the head tilted downward and the hind limbs totally unloaded. A progressive decrease in the size of the soleus muscle from suspended rats was observed as a function of time. The rate of protein degradation of the homogenates from the soleus muscles of suspended and control animals was not significantly different. The rate of cell-free protein synthesis was severely repressed in the atrophied muscle. An initial rise in the levels of plasma glucose and corticosterone was observed on the second day of suspension, but they subsequently returned to normal values.

  16. Three Intermittent Sessions of Cryotherapy Reduce the Secondary Muscle Injury in Skeletal Muscle of Rat

    PubMed Central

    Oliveira, Nuno M. L.; Rainero, Elaine P.; Salvini, Tania F.

    2006-01-01

    Although cryotherapy associated to compression is recommended as immediate treatment after muscle injury, the effect of intermittent sessions of these procedures in the area of secondary muscle injury is not established. This study examined the effect of three sessions of cryotherapy (30 min of ice pack each 2h) and muscle compression (sand pack) in the muscle-injured area. Twenty-four Wistar rats (312 ± 20g) were evaluated. In three groups, the middle belly of tibialis anterior (TA) muscle was injured by a frozen iron bar and received one of the following treatments: a) three sessions of cryotherapy; b) three sessions of compression; c) not treated. An uninjured group received sessions of cryotherapy. Frozen muscles were cross- sectioned (10 µm) and stained for the measurement of injured and uninjured muscle area. Injured muscles submitted to cryotherapy showed the smallest injured area (29.83 ± 6.6%), compared to compressed (39.2 ± 2.8%, p= 0.003) and untreated muscles (41.74 ± 4.0%, p = 0.0008). No difference was found between injured compressed and injured untreated muscles. In conclusion, three intermittent sessions of cryotherapy applied immediately after muscle damage was able to reduce the secondary muscle injury, while only the muscle compression did not provide the same effectiveness. Key Points Three sessions of cryotherapy (30 min each 2 hours) applied immediately after muscle damage reduce the secondary muscle injury. Sessions of compression applied after muscle damage are not able to reduce the secondary muscle injury. PMID:24259995

  17. Functional characteristics of the rat jaw muscles: daily muscle activity and fiber type composition.

    PubMed

    Kawai, Nobuhiko; Sano, Ryota; Korfage, Joannes A M; Nakamura, Saika; Tanaka, Eiji; van Wessel, Tim; Langenbach, Geerling E J; Tanne, Kazuo

    2009-12-01

    Skeletal muscles have a heterogeneous fiber type composition, which reflects their functional demand. The daily muscle use and the percentage of slow-type fibers have been shown to be positively correlated in skeletal muscles of larger animals but for smaller animals there is no information. The examination of this relationship in adult rats was the purpose of this study. We hypothesized a positive relationship between the percentage of fatigue-resistant fibers in each muscle and its total duration of use per day. Fourteen Wistar strain male rats (410-450 g) were used. A radio-telemetric device was implanted to record muscle activity continuously from the superficial masseter, deep masseter, anterior belly of digastric and anterior temporalis muscles. The degree of daily muscle use was quantified by the total duration of muscle activity per day (duty time) exceeding specified levels of the peak activity (2, 5, 20 and 50%). The fiber type composition of the muscles was examined by the myosin heavy chain content of the fibers by means of immunohistochemical staining. At lower activity levels (exceeding 2 and 5% of the peak activity), the duty time of the anterior belly of digastric muscle was significantly (P < 0.01) longer than those of the other muscles. The anterior belly of digastric muscle also contained the highest percentage of slow-type fibers (type I fiber and hybrid fiber co-expressing myosin heavy chain I + IIA) (ca. 11%; P < 0.05). By regression analysis for all four muscles, an inter-muscular comparison showed a positive relationship between the duty time (exceeding 50% of the peak activity) and the percentage of type IIX fibers (P < 0.05), which demonstrate intermediate physiological properties relative to type IIA and IIB fibers. For the jaw muscles of adult male rats, the variations of fiber type composition and muscle use suggest that the muscle containing the largest amounts of slow-type fibers (the anterior belly of digastric muscle) is mainly

  18. Muscle contractile activity regulates Sirt3 protein expression in rat skeletal muscles.

    PubMed

    Hokari, Fumi; Kawasaki, Emi; Sakai, Atsushi; Koshinaka, Keiichi; Sakuma, Kunihiro; Kawanaka, Kentaro

    2010-08-01

    Sirt3, a member of the sirtuin family, is known to control cellular mitochondrial function. Furthermore, because sirtuins require NAD for their deacetylase activity, nicotinamide phosphoribosyltransferase (Nampt), which is a rate-limiting enzyme in the intracellular NAD biosynthetic pathway, influences their activity. We examined the effects of exercise training and normal postural contractile activity on Sirt3 and Nampt protein expression in rat skeletal muscles. Male rats were trained by treadmill running at 20 m/min, 60 min/day, 7 days/wk for 4 wk. This treadmill training program increased the Sirt3 protein expression in the soleus and plantaris muscles by 49% and 41%, respectively (P < 0.05). Moreover, a 4-wk voluntary wheel-running program also induced 66% and 95% increases in Sirt3 protein in the plantaris and triceps muscles of rats, respectively (P < 0.05). Treadmill-running and voluntary running training induced no significant changes in Nampt protein expression in skeletal muscles. In resting rats, the soleus muscle, which is recruited during normal postural activity, possessed the greatest expression levels of the Sirt3 and Nampt proteins, followed by the plantaris and triceps muscles. Furthermore, the Sirt3, but not Nampt, protein level was reduced in the soleus muscles from immobilized hindlimbs compared with that shown in the contralateral control muscle. These results demonstrated that 1) Sirt3 protein expression is upregulated by exercise training in skeletal muscles and 2) local postural contractile activity plays an important role in maintaining a high level of Sirt3 protein expression in postural muscle.

  19. Sumoylated α-skeletal muscle actin in the skeletal muscle of adult rats.

    PubMed

    Uda, Munehiro; Kawasaki, Hiroaki; Iizumi, Kyoichi; Shigenaga, Ayako; Baba, Takeshi; Naito, Hisashi; Yoshioka, Toshitada; Yamakura, Fumiyuki

    2015-11-01

    Skeletal muscles are composed of two major muscle fiber types: slow-twitch oxidative fibers and fast-twitch glycolytic fibers. The proteins in these muscle fibers are known to differ in their expression, relative abundance, and post-translational modifications. In this study, we report a previously unreported post-translational modification of α-skeletal muscle actin in the skeletal muscles of adult male F344 rats in vivo. Using two-dimensional electrophoresis (2D-PAGE), we first examined the differences in the protein expression profiles between the soleus and plantaris muscles. We found higher intensity protein spots at approximately 60 kDa and pH 9 on 2D-PAGE for the soleus muscle compared with the plantaris muscle. These spots were identified as α-skeletal muscle actin by liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry and western blot analyses. In addition, we found that the 60 kDa α-skeletal muscle actin is modified by small ubiquitin-like modifier (SUMO) 1, using 2D-PAGE and western blot analyses. Furthermore, we found that α-skeletal muscle actin with larger molecular weight was localized in the nuclear and cytosol of the skeletal muscle, but not in the myofibrillar fraction by the combination of subcellular fractionation and western blot analyses. These results suggest that α-skeletal muscle actin is modified by SUMO-1 in the skeletal muscles, localized in nuclear and cytosolic fractions, and the extent of this modification is much higher in the slow muscles than in the fast muscles. This is the first study to show the presence of SUMOylated actin in animal tissues.

  20. Calcium overload increases oxidative stress in old rat gastrocnemius muscle.

    PubMed

    Capel, F; Demaison, L; Maskouri, F; Diot, A; Buffiere, C; Patureau Mirand, P; Mosoni, L

    2005-09-01

    In order to challenge in vivo muscle Ca2+ homeostasis and analyze consequences on mitochondrial H2O2 release (MHR) and sarcopenia, we injected Ca2+ ionophore A23187 (200 microg/kg, ip) in adult and old rats and measured gastrocnemius mass and mitochondrial Ca2+ content (MCC) using radioactive Ca2+ 48 h after injection. In a second experiment performed in old rats, we measured isocitrate dehydrogenase (ICDH) activity as an index of MCC, MHR, mitochondrial respiration, citrate synthase, COX and antioxydant enzyme activities 24 h after a 150 microg/kg injection. In adult rats, muscle mass and MCC were unchanged by A23187. In old rats, MCC increased 24 h after injection as reflected by a significant increase in ICDH activity; measured MCC tended to increase at 48 h. MHR and Mn-SOD activity were significantly increased at 24 h, and GPX activity was reduced. Muscle mass was unchanged but was negatively correlated with MCC in control and treated old rats. In conclusion, in old rats, A23187 probably induced a mitochondrial Ca2+ overload responsible for the observed increase in MHR without leading to muscle atrophy on a short term basis.

  1. Reduction-oxidation state and protein degradation in skeletal muscle of fasted and refed rats

    NASA Technical Reports Server (NTRS)

    Fagan, Julie M.; Tischler, Marc E.

    1986-01-01

    Redox state and protein degradation were measured in isolated muscles of fasted (up to 10 d) and refed (up to 4 d) 7- to 14-wk-old rats. Protein degradation in the extensor digitorum longus muscle, but not in the soleus muscle, was greater in the fasted rats than in weight-matched muscle from fed rats. The NAD couple was more oxidized in incubated and fresh extensor digitorum longus muscles and in some incubated soleus muscles of fasted rats than in weight-matched muscle from fed rats. In the extensor digitorum longus muscle of refed or prolonged fasted rats, protein degradation was slower and the NAD couple was more reduced than in the fed state. Therefore, oxidation of the NAD couple was associated with increased muscle breakdown during fasting, whereas reduction of the NAD couple was associated with muscle conservation and deposition.

  2. Ultrastructural alterations in skeletal muscle fibers of rats after exercise

    NASA Technical Reports Server (NTRS)

    Akuzawa, M.; Hataya, M.

    1982-01-01

    Ultrastructural alterations in skeletal muscle fibers were electron microscopically studied in rats forced to run on the treadmill until all-out. When they were mild and limited to relatively small areas, the reconstruction of filaments ensued within 10 days without infiltration of cells. When they were severe and extensive, phagocytes infiltrated in the lesions and removed degenerative sacroplasmic debris from muscle fibers. A little later, myoblasts appeared and regeneration was accomplished in 30 days in much the same manner as in myogenesis.

  3. Endogenous L-Carnosine Level in Diabetes Rat Cardiac Muscle

    PubMed Central

    Liu, Yali; Su, Dan; Zhang, Ling; Wei, Shaofeng; Liu, Kuangyi; Peng, Mi; Li, Hanyun; Song, Yonggui

    2016-01-01

    A novel method for quantitation of cardiac muscle carnosine levels using HPLC-UV is described. In this simple and reliable method, carnosine from the rat cardiac muscle and the internal standard, thymopentin, were extracted by protein precipitation with acetonitrile. The method was linear up to 60.96 μg·mL−1 for L-carnosine. The calibration curve was linear in concentration ranges from 0.5 to 60.96 μg·mL−1. The relative standard deviations obtained for intra- and interday precision were lower than 12% and the recoveries were higher than 90% for both carnosine and internal standard. We successfully applied this method to the analysis of endogenous carnosine in cardiac muscle of the diabetes rats and healthy control rats. The concentration of carnosine was significantly lower in the diabetes rats group, compared to that in the healthy control rats. These results support the usefulness of this method as a means of quantitating carnosine and illustrate the important role of L-carnosine in cardiac muscle. PMID:27190533

  4. Endurance training facilitates myoglobin desaturation during muscle contraction in rat skeletal muscle.

    PubMed

    Takakura, Hisashi; Furuichi, Yasuro; Yamada, Tatsuya; Jue, Thomas; Ojino, Minoru; Hashimoto, Takeshi; Iwase, Satoshi; Hojo, Tatsuya; Izawa, Tetsuya; Masuda, Kazumi

    2015-03-24

    At onset of muscle contraction, myoglobin (Mb) immediately releases its bound O2 to the mitochondria. Accordingly, intracellular O2 tension (PmbO2) markedly declines in order to increase muscle O2 uptake (mVO2). However, whether the change in PmbO2 during muscle contraction modulates mVO2 and whether the O2 release rate from Mb increases in endurance-trained muscles remain unclear. The purpose of this study was, therefore, to determine the effect of endurance training on O2 saturation of Mb (SmbO2) and PmbO2 kinetics during muscle contraction. Male Wistar rats were subjected to a 4-week swimming training (Tr group; 6 days per week, 30 min × 4 sets per day) with a weight load of 2% body mass. After the training period, deoxygenated Mb kinetics during muscle contraction were measured using near-infrared spectroscopy under hemoglobin-free medium perfusion. In the Tr group, the VmO2peak significantly increased by 32%. Although the PmbO2 during muscle contraction did not affect the increased mVO2 in endurance-trained muscle, the O2 release rate from Mb increased because of the increased Mb concentration and faster decremental rate in SmbO2 at the maximal twitch tension. These results suggest that the Mb dynamics during muscle contraction are contributing factors to faster VO2 kinetics in endurance-trained muscle.

  5. The ischiourethralis muscle of the rat: anatomy, innervation, and function.

    PubMed

    Dail, W G; Sachs, B D

    1991-02-01

    The ischiourethralis (IU), a striated perineal muscle presumed to be involved in sexual reflexes, was studied in the rat. The paired muscle arises from the penile crus and the penile bulb and unites in a raphe over the deep dorsal vein of the penis. Retrograde tracing studies show that the muscle is innervated by neurons in the dorsolateral nucleus of the lumbar spinal cord, a pudendal nerve motor nucleus which also innervates the ischiocavernosus muscle. Excision of the IU muscle did not interfere with the ability of males to display normal copulatory behavior, nor did it affect significantly the number and intensity of reflexive erections. It nevertheless remains possible that the IU may contribute to intense glans erection by compressing the deep dorsal vein.

  6. A Rat Model for Muscle Regeneration in the Soft Palate

    PubMed Central

    Carvajal Monroy, Paola L.; Grefte, Sander; Kuijpers-Jagtman, Anne M.; Helmich, Maria P. A. C.; Ulrich, Dietmar J. O.; Von den Hoff, Johannes W.; Wagener, Frank A. D. T. G.

    2013-01-01

    Background Children with a cleft in the soft palate have difficulties with speech, swallowing, and sucking. Despite successful surgical repositioning of the muscles, optimal function is often not achieved. Scar formation and defective regeneration may hamper the functional recovery of the muscles after cleft palate repair. Therefore, the aim of this study is to investigate the anatomy and histology of the soft palate in rats, and to establish an in vivo model for muscle regeneration after surgical injury. Methods Fourteen adult male Sprague Dawley rats were divided into four groups. Groups 1 (n = 4) and 2 (n = 2) were used to investigate the anatomy and histology of the soft palate, respectively. Group 3 (n = 6) was used for surgical wounding of the soft palate, and group 4 (n = 2) was used as unwounded control group. The wounds (1 mm) were evaluated by (immuno)histochemistry (AZAN staining, Pax7, MyoD, MyoG, MyHC, and ASMA) after 7 days. Results The present study shows that the anatomy and histology of the soft palate muscles of the rat is largely comparable with that in humans. All wounds showed clinical evidence of healing after 7 days. AZAN staining demonstrated extensive collagen deposition in the wound area, and initial regeneration of muscle fibers and salivary glands. Proliferating and differentiating satellite cells were identified in the wound area by antibody staining. Conclusions This model is the first, suitable for studying muscle regeneration in the rat soft palate, and allows the development of novel adjuvant strategies to promote muscle regeneration after cleft palate surgery. PMID:23554995

  7. Rat rotator cuff muscle responds differently from hindlimb muscle to a combined tendon-nerve injury.

    PubMed

    Davies, Michael R; Ravishankar, Bharat; Laron, Dominique; Kim, Hubert T; Liu, Xuhui; Feeley, Brian T

    2015-07-01

    Rotator cuff tears (RCTs) are among the most common musculoskeletal injuries seen by orthopaedic surgeons. Clinically, massive cuff tears lead to unique pathophysiological changes in rotator cuff muscle, including atrophy, and massive fatty infiltration, which are rarely seen in other skeletal muscles. Studies in a rodent model for RCT have demonstrated that these histologic findings are accompanied by activation of the Akt/mammalian target of rapamycin (mTOR) and transforming growth factor-β (TGF-β) pathways following combined tendon-nerve injury. The purpose of this study was to compare the histologic and molecular features of rotator cuff muscle and gastrocnemius muscle--a major hindlimb muscle, following combined tendon-nerve injury. Six weeks after injury, the rat gastrocnemius did not exhibit notable fatty infiltration compared to the rotator cuff. Likewise, the adipogenic markers SREBP-1 and PPARγ as well as the TGF-β canonical pathway were upregulated in the rotator cuff, but not the gastrocnemius. Our study suggests that the rat rotator cuff and hindlimb muscles differ significantly in their response to a combined tendon-nerve injury. Clinically, these findings highlight the unique response of the rotator cuff to injury, and may begin to explain the poor outcomes of massive RCTs compared to other muscle-tendon injuries.

  8. Reference values of respiratory and peripheral muscle function in rats.

    PubMed

    Barreiro, E; Marín-Corral, J; Sanchez, F; Mielgo, V; Alvarez, F J; Gáldiz, J B; Gea, J

    2010-12-01

    Skeletal muscle dysfunction is a common systemic manifestation in several prevalent diseases. Predictive values are useful tools for the diagnosis and prognosis of diseases. In experimental animals, no reference values of muscle function evaluation have been so far reported. The objective was to obtain predictive values of maximal inspiratory pressure (MIP) and grip strength measurements in healthy rats. In 70 healthy rats, MIP and grip strength were measured in vivo weekly for five consecutive weeks using non-invasive methodologies. Three ranges of rat body weights (250-299, 300-349 and 350-399 g) and lengths (37.0-41.0, 41.1-42.0 and 42.1-44.0 cm) were established. MIP and grip strength measurements falling within the ranges of weight 350-399 and 300-349 g and length 42.1-44.0 cm were significantly greater than values falling within 250-299 g and 37.0-41.0 cm ranges respectively. Specific weight- and length-percentile distributions for MIP and grip strength measurements were calculated. As significant direct correlations were observed between rat weights and lengths and either MIP or grip strength measurements, regression equations relating all these variables were also determined. Skeletal muscle dysfunction is frequently associated with highly prevalent conditions. The significant predictive equations described for both MIP and grip strength measurements will enable scientists to better estimate the respiratory and peripheral muscle dysfunctions of laboratory animals, especially when conducting follow-up and/or intervention investigations.

  9. Establishment of bipotent progenitor cell clone from rat skeletal muscle.

    PubMed

    Murakami, Yousuke; Yada, Erica; Nakano, Shin-ichi; Miyagoe-Suzuki, Yuko; Hosoyama, Tohru; Matsuwaki, Takashi; Yamanouchi, Keitaro; Nishihara, Masugi

    2011-12-01

    The present study describes the isolation, cloning and characterization of adipogenic progenitor cells from rat skeletal muscle. Among the obtained 10 clones, the most highly adipogenic progenitor, 2G11 cells, were further characterized. In addition to their adipogenicity, 2G11 cells retain myogenic potential as revealed by formation of multinucleated myotubes when co-cultured with myoblasts. 2G11 cells were resistant to an inhibitory effect of basic fibroblast growth factor on adipogenesis, while adipogenesis of widely used preadipogenic cell line, 3T3-L1 cells, was suppressed almost completely by the same treatment. In vivo transplantation experiments revealed that 2G11 cells are able to possess both adipogenicity and myogenicity in vivo. These results indicate the presence of bipotent progenitor cells in rat skeletal muscle, and suggest that such cells may contribute to ectopic fat formation in skeletal muscle.

  10. Bone and muscle atrophy with suspension of the rat

    NASA Technical Reports Server (NTRS)

    Leblanc, A.; Marsh, C.; Evans, H.; Johnson, P.; Schneider, V.; Jhingran, S.

    1985-01-01

    In order to identify a suitable model for the study of muscle atrophy due to suspension in space, a modified version of the Morey tail suspension model was used to measure the atrophic responses of rat bone and muscle to 14-30 days of unloading of the hindlimbs. The progress of atrophy was measured by increases in methylene diphosphonate (MDP) uptake. It is found that bone uptake of methylene diphosphonate followed a phasic pattern similar to changes in the bone formation rate of immobilized dogs and cats. Increased MDP uptake after a period of 60 days indicated an accelerated bone metabolism. Maximum muscle atrophy in the suspended rats was distinctly different from immobilization atrophy. On the basis of the experimental results, it is concluded that the tail suspension model is an adequate simulation of bone atrophy due to suspension.

  11. Compensatory effects of chronic electrostimulation on unweighted rat soleus muscle.

    PubMed

    Leterme, D; Falempin, M

    1994-01-01

    The purpose of this study was to investigate the effects of electrostimulation in counteracting the transformation of the unweighted rat soleus muscle. The stimulation resembled the firing patterns of normal slow motor units and was imposed during hindlimb suspension. For the 10-day hindlimb suspended rats, the transformation of the slow soleus muscle towards a faster type was characterized by a decrease in the time to peak tension and the half-relaxation time of the twitch, a reduction in the P20/P0 index, i.e. the ratio of the subtetanic tension at 20 Hz relative to the tetanic tension, and a decrease in the percentage distributions of type I fibres accompanied by an increase of type IIa and IIc fibres. These changes were prevented by electrostimulation since, for the parameters mentioned above, no significant difference was observed in the soleus of the suspended rats that received electrostimulation when compared with the control rats. Nevertheless, neither the loss of mass nor the decrease in force output in the suspended rats were prevented by electrostimulation. The present results suggest a positive compensation of the suspension-induced alterations in the contractile and histochemical properties of the soleus muscle by means of chronic electrostimulation, which, however, do not prevent atrophy or the loss of contractile force.

  12. Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles

    NASA Technical Reports Server (NTRS)

    Max, Stephen R.; Konagaya, Masaaki; Konagaya, Yoko; Thomas, John W.; Banner, Carl; Vitkovic, Ljubisa

    1986-01-01

    The regulation of glutamine synthetase by glucocorticoids in rat skeletal muscles was studied. Administration of dexamethasone strikingly enhanced glutamine synthetase activity in plantaris and soleus muscles. The dexamethasone-mediated induction of glutamine synthetase activity was blocked to a significant extent by orally administered RU38486, a glucocorticoid antagonist, indicating the involvement of intracellular glucocorticoid receptors in the induction. Northern blot analysis revealed that dexamethasone-mediated enhancement of glutamine synthetase activity involves dramatically increased levels of glutamine synthetase mRNA. The induction of glutamine synthetase was selective in that glutaminase activity of soleus and plantaris muscles was not increased by dexamethasone. Furthermore, dexamethasone treatment resulted in only a small increase in glutamine synthetase activity in the heart. Accordingly, there was only a slight change in glutamine synthetase mRNA level in this tissue. Thus, glucocorticoids regulate glutamine synthetase gene expression in rat muscles at the transcriptional level via interaction with intracellular glutamine production by muscle and to mechanisms underlying glucocorticoid-induced muscle atrophy.

  13. Angiotensin II induces differential insulin action in rat skeletal muscle.

    PubMed

    Surapongchai, Juthamard; Prasannarong, Mujalin; Bupha-Intr, Tepmanas; Saengsirisuwan, Vitoon

    2017-03-01

    Angiotensin II (ANGII) is reportedly involved in the development of skeletal muscle insulin resistance. The present investigation evaluated the effects of two ANGII doses on the phenotypic characteristics of insulin resistance syndrome and insulin action and signaling in rat skeletal muscle. Male Sprague-Dawley rats were infused with either saline (SHAM) or ANGII at a commonly used pressor dose (100 ng/kg/min; ANGII-100) or a higher pressor dose (500 ng/kg/min; ANGII-500) via osmotic minipumps for 14 days. We demonstrated that ANGII-100-infused rats exhibited the phenotypic features of non-obese insulin resistance syndrome, including hypertension, impaired glucose tolerance and insulin resistance of glucose uptake in the soleus muscle, whereas ANGII-500-treated rats exhibited diabetes-like symptoms, such as post-prandial hyperglycemia, impaired insulin secretion and hypertriglyceridemia. At the cellular level, insulin-stimulated glucose uptake in the soleus muscle of the ANGII-100 group was 33% lower (P < 0.05) than that in the SHAM group and was associated with increased insulin-stimulated IRS-1 Ser(307) and decreased Akt Ser(473) and AS160 Thr(642) phosphorylation and GLUT-4 expression. However, ANGII-500 infusion did not induce skeletal muscle insulin resistance or impair insulin signaling elements as initially anticipated. Moreover, we found that insulin-stimulated glucose uptake in the ANGII-500 group was accompanied by the enhanced expression of ACE2 and MasR proteins, which are the key elements in the non-classical pathway of the renin-angiotensin system. Collectively, this study demonstrates for the first time that chronic infusion with these two pressor doses of ANGII induced differential metabolic responses at both the systemic and skeletal muscle levels.

  14. Brainstem cholinergic modulation of muscle tone in infant rats.

    PubMed

    Gall, Andrew J; Poremba, Amy; Blumberg, Mark S

    2007-06-01

    In week-old rats, lesions of the dorsolateral pontine tegmentum (DLPT) and nucleus pontis oralis (PnO) have opposing effects on nuchal muscle tone. Specifically, pups with DLPT lesions exhibit prolonged bouts of nuchal muscle atonia (indicative of sleep) and pups with PnO lesions exhibit prolonged bouts of high nuchal muscle tone (indicative of wakefulness). Here we test the hypothesis that nuchal muscle tone is modulated, at least in part, by cholinergically mediated interactions between these two regions. First, in unanesthetized pups, we found that chemical infusion of the cholinergic agonist carbachol (22 mm, 0.1 microL) within the DLPT produced high muscle tone. Next, chemical lesions of the PnO were used to produce a chronic state of high nuchal muscle tone, at which time the cholinergic antagonist scopolamine (10 mm, 0.1 microL) was infused into the DLPT. Scopolamine effectively decreased nuchal muscle tone, thus suggesting that lesions of the PnO increase muscle tone via cholinergic activation of the DLPT. Using 2-deoxyglucose autoradiography, metabolic activation throughout the DLPT was observed after PnO lesions. Finally, consistent with the hypothesis that PnO inactivation produces high muscle tone, infusion of the sodium channel blocker lidocaine (2%) into the PnO of unanesthetized pups produced rapid increases in muscle tone. We conclude that, even early in infancy, the DLPT is critically involved in the regulation of muscle tone and behavioral state, and that its activity is modulated by a cholinergic mechanism that is directly or indirectly controlled by the PnO.

  15. Classification of muscle spindle afferents innervating the masseter muscle in rats.

    PubMed

    Masri, Radi; Ro, Jin Y; Dessem, Dean; Capra, Norman

    2006-09-01

    Taylor et al. [Taylor, A., Durbaba, R., Rodgers, J.F., 1992a. The classification of afferents from muscle spindles of the jaw-closing muscles of the cat. J Physiol 456, 609-628] developed a method to classify muscle spindle afferents using succinylcholine (Sch) and ramp and hold stretches. They demonstrated that cat jaw muscle spindle afferents show high proportion of intermediate responses to ramp and hold jaw stretch. Together with observations on the responses to Sch their data suggests that the majority of jaw muscle spindle afferents are influenced by a combination of nuclear bag(2) and nuclear chain fibres. Relatively few are influenced solely by nuclear bag(1) fibres. The purpose of this study was to categorize jaw muscle spindle afferent in rodents in response to ramp and hold stretches. Several measures were used to classify spindle afferents including (1) conduction velocity, (2) coefficient of variation (C.V.) of the interspike interval during jaw opening, and (3) the dynamic sensitivity and the initial discharge of spindle afferents before and after succinylcholine infusion (Sch, 100mg/kg, i.v.). Consistent with observations in the cat jaw muscles, the distribution of the conduction velocity and the C.V. of Vmes masseter afferents were unimodal. Therefore, these parameters were of little value in functional classification of spindle innervation. Succinylcholine injection either markedly increased the dynamic sensitivity or produced no change in Vmes afferents. Unlike cat jaw muscle spindle afferents, the effect of Sch on the initial discharge was not clearly separable from those responding or not responding to Sch. These results suggest that rat jaw muscle spindle afferents, have physiological properties that are primarily intermediate in nature and are likely to reflect a predominance of influence from nuclear bag(2) and chain fibres. However, the distinction between bag(2) and chain fibres influences is not as clearly defined in the rat compared to

  16. Acid phosphatase and protease activities in immobilized rat skeletal muscles

    NASA Technical Reports Server (NTRS)

    Witzmann, F. A.; Troup, J. P.; Fitts, R. H.

    1982-01-01

    The effect of hind-limb immobilization on selected Iysosomal enzyme activities was studied in rat hing-limb muscles composed primarily of type 1. 2A, or 2B fibers. Following immobilization, acid protease and acid phosphatase both exhibited signifcant increases in their activity per unit weight in all three fiber types. Acid phosphatase activity increased at day 14 of immobilization in the three muscles and returned to control levels by day 21. Acid protease activity also changed biphasically, displaying a higher and earlier rise than acid phosphatase. The pattern of change in acid protease, but not acid phosphatase, closely parallels observed muscle wasting. The present data therefore demonstrate enhanced proteolytic capacity of all three fiber types early during muscular atrophy. In addition, the data suggest a dependence of basal hydrolytic and proteolytic activities and their adaptive response to immobilization on muscle fiber composition.

  17. Sex steroids do not affect muscle weight, oxidative metabolism or cytosolic androgen reception binding of functionally overloaded rat Plantaris muscles

    NASA Technical Reports Server (NTRS)

    Max, S. R.; Rance, N.

    1983-01-01

    The effects of sex steroids on muscle weight and oxidative capacity of rat planaris muscles subjected to functional overload by removal of synergistic muscles were investigated. Ten weeks after bilateral synergist removal, plantaris muscles were significantly hypertrophic compared with unoperated controls. After this period, the ability of the muscles to oxide three substrates of oxidative metabolism was assessed. Experimental procedures are discussed and results are presented herein. Results suggest a lack of beneficial effect of sex hormone status on the process of hypertrophy and on biochemical changes in overloaded muscle. Such findings are not consistent with the idea of synergistic effects of sex steroids and muscle usage.

  18. Proteomic Profiling of Rat Thyroarytenoid Muscle

    ERIC Educational Resources Information Center

    Welham, Nathan V.; Marriott, Gerard; Bless, Diane M.

    2006-01-01

    Purpose: Proteomic methodologies offer promise in elucidating the systemwide cellular and molecular processes that characterize normal and diseased thyroarytenoid (TA) muscle. This study examined methodological issues central to the application of 2-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (2D SDS-PAGE) to the study of…

  19. Mitochondria-associated apoptotic signalling in denervated rat skeletal muscle

    PubMed Central

    Siu, Parco M; Alway, Stephen E

    2005-01-01

    Apoptosis has been implicated in the regulation of denervation-induced muscle atrophy. However, the activation of apoptotic signal transduction during muscle denervation has not been fully elucidated. The present study examined the apoptotic responses to denervation in rat gastrocnemius muscle. Following 14 days of denervation, the extent of apoptotic DNA fragmentation as determined by a cytosolic nucleosome ELISA was increased by 100% in the gastrocnemius muscle. RT-PCR and immunoblot analyses indicated that Bax was dramatically upregulated while Bcl-2 was modestly increased; however, the Bax/Bcl-2 ratio was significantly increased in denervated muscles relative to control muscles. Analyses of ELISA and immunoblots from mitochondria-free cytosol extracts showed a significant increase in mitochondria-associated apoptotic factors, including cytochrome c, Smac/DIABLO and apoptosis-inducing factor (AIF). In addition to the upregulation of caspase-3 and -9 mRNA, pro-/cleaved caspase protein and proteolytic activity levels, the X-linked inhibitor of apoptosis (XIAP) protein level was downregulated. The cleaved product of poly(ADP-ribose) polymerase (PARP) was detected in muscle samples following denervation. Although we did not find a difference in the inhibitor of DNA binding/ differentiation-2 (Id2) and c-Myc protein contents between the denervated and control muscles, the protein content of tumour suppressor p53 was significantly increased in both the nuclear and the cytosolic fractions with denervation. Moreover, denervation increased the protein content of HSP70, whereas the MnSOD (a mitochondrial isoform of superoxide dismutase) protein content was diminished, which indicated that denervation might have induced cellular and/or oxidative stress. Our data show that mitochondria-associated apoptotic signalling is upregulated during muscle denervation. We interpret these findings to indicate that apoptosis has a physiologically important role in regulating denervation

  20. An evaluation of the reliability of muscle fiber cross-sectional area and fiber number measurements in rat skeletal muscle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The reliability of estimating muscle fiber cross-sectional area (measure of muscle fiber size) and fiber number from only a subset of fibers in rat hindlimb muscle cross-sections has not been systematically evaluated. This study examined the variability in mean estimates of fiber cross-s...

  1. Dissemination of Walker 256 carcinoma cells to rat skeletal muscle

    SciTech Connect

    Ueoka, H.; Hayashi, K.; Namba, T.; Grob, D.

    1986-03-05

    After injection of 10/sup 6/ Walker 256 carcinoma cells labelled with /sup 125/I-5-iodo-2'-deoxyuridine into the tail vein, peak concentration in skeletal muscle was 46 cells/g at 60 minutes, which was lower than 169202, 1665, 555, 198 and 133 cells/g, respectively, at 30 or 60 minutes in lung, liver, spleen, kidney and heart. Because skeletal muscle constitutes 37.4% of body weight, the total number of tumor cells was 2323 cells, which was much greater than in spleen, kidney and heart with 238, 271, and 85 cells, respectively, and only less than in lung and liver, at 222857 and 11700 cells, respectively. The total number in skeletal muscle became greater than in liver at 4 hours and than in lung at 24 hours. Ten minutes after injection of 7.5 x 10/sup 6/ Walker 256 carcinoma cells into the abdominal aorta of rats, a mean of 31 colony-forming cells were recovered from the gastrocnemius, while 106 cells were recovered from the lung after injection into the tail vein. These results indicate that a large number of viable tumor cells can be arrested in skeletal muscle through circulation. The rare remote metastasis of malignancies into skeletal muscle despite constantly circulating tumor cells does not appear to be due to poor dissemination of tumor cells into muscle but due to unhospitable environment of skeletal muscle.

  2. Effects of taurine administration in rat skeletal muscles on exercise.

    PubMed

    Yatabe, Yoshihisa; Miyakawa, Shumpei; Miyazaki, Teruo; Matsuzaki, Yasushi; Ochiai, Naoyuki

    2003-01-01

    To investigate the effects of taurine administration on exercise, we studied taurine concentrations in rat skeletal muscles after endurance running and the duration of running time to exhaustion, with and without taurine administration. For study 1 we divided 40 male SD rats into two groups: endurance exercise group ( n = 20) and sedentary control group ( n = 20). Each was further divided into two groups; one received distilled water ( n = 10) and the other taurine solution in water 0.5 g/kg/day orally ( n = 10) for 2 weeks. The exercise group performed treadmill running (60 min) once only after their nursing period. For study 2, we divided 10 male SD rats into two groups; one ( n = 5) received taurine 0.5 g/kg/day, and the other ( n = 5) received no taurine for 2 weeks; the two groups then performed treadmill running to exhaustion. In study 1, taurine administration increased taurine concentrations in leg skeletal muscles, whereas the concentrations were significantly lower in the exercised groups without taurine administration. Taurine administration reduced the decrease in taurine concentration in skeletal muscles on exercise. In study 2, the duration of running time to exhaustion was significantly increased by taurine administration. We concluded that peroral administration of taurine maintains the taurine concentration in skeletal muscle on exercise and up-regulates physical endurance.

  3. Rat hindlimb muscle responses to suspension hypokinesia/hypodynamia

    NASA Technical Reports Server (NTRS)

    Musacchia, X. J.; Steffen, J. M.; Deavers, D. R.

    1983-01-01

    Hypokinetic/hyupodynamic (H/H) whole body suspension of rats eliminates hindlimb load bearing functions while permitting continued use of the forelimbs. Responses of hindlimb muscles were assessed in terms of absolute and relative weights during 1 and 2 weeks of H/H suspension. Muscle mass loss was in the order soleus greater than gastrocnemius equal to plantaris greater than extensor digitorum longus (EDL). The soleus, a postural antigravity muscle composed mainly of slow twitch fibers, was most sensitive, losing 35 and 45 percent of its weight during the first and second weeks, respectively. The gastrocnemius and plantaris showed losses during the first week but no significant loss during the second wee. The EDL showed little or no weight loss. During post suspension recovery all muscles showed a weight gain. H/H suspended rats failed to grow; following removal from suspension they gained weight linearly, comparable to controls. Products of muscle metabolism including urea, ammonia, and 3-methylhistidine increased in the urine during H/H suspension and were significantly reduced approaching control levels during recovery. This suspension model offers considerable promise for comparison with H/H responses during weightlessness.

  4. Manual therapy ameliorates delayed-onset muscle soreness and alters muscle metabolites in rats.

    PubMed

    Urakawa, Susumu; Takamoto, Kouichi; Nakamura, Tomoya; Sakai, Shigekazu; Matsuda, Teru; Taguchi, Toru; Mizumura, Kazue; Ono, Taketoshi; Nishijo, Hisao

    2015-02-01

    Delayed-onset muscle soreness (DOMS) can be induced by lengthening contraction (LC); it can be characterized by tenderness and movement-related pain in the exercised muscle. Manual therapy (MT), including compression of exercised muscles, is widely used as physical rehabilitation to reduce pain and promote functional recovery. Although MT is beneficial for reducing musculoskeletal pain (i.e. DOMS), the physiological mechanisms of MT remain unclear. In the present study, we first developed an animal model of MT in DOMS; LC was applied to the rat gastrocnemius muscle under anesthesia, which induced mechanical hyperalgesia 2-4 days after LC. MT (manual compression) ameliorated mechanical hyperalgesia. Then, we used capillary electrophoresis time-of-flight mass spectroscopy (CE-TOFMS) to investigate early effects of MT on the metabolite profiles of the muscle experiencing DOMS. The rats were divided into the following three groups; (1) normal controls, (2) rats with LC application (LC group), and (3) rats undergoing MT after LC (LC + MT group). According to the CE-TOFMS analysis, a total of 171 metabolites were detected among the three groups, and 19 of these metabolites were significant among the groups. Furthermore, the concentrations of eight metabolites, including branched-chain amino acids, carnitine, and malic acid, were significantly different between the LC + MT and LC groups. The results suggest that MT significantly altered metabolite profiles in DOMS. According to our findings and previous data regarding metabolites in mitochondrial metabolism, the ameliorative effects of MT might be mediated partly through alterations in metabolites associated with mitochondrial respiration.

  5. Manual therapy ameliorates delayed-onset muscle soreness and alters muscle metabolites in rats

    PubMed Central

    Urakawa, Susumu; Takamoto, Kouichi; Nakamura, Tomoya; Sakai, Shigekazu; Matsuda, Teru; Taguchi, Toru; Mizumura, Kazue; Ono, Taketoshi; Nishijo, Hisao

    2015-01-01

    Delayed-onset muscle soreness (DOMS) can be induced by lengthening contraction (LC); it can be characterized by tenderness and movement-related pain in the exercised muscle. Manual therapy (MT), including compression of exercised muscles, is widely used as physical rehabilitation to reduce pain and promote functional recovery. Although MT is beneficial for reducing musculoskeletal pain (i.e. DOMS), the physiological mechanisms of MT remain unclear. In the present study, we first developed an animal model of MT in DOMS; LC was applied to the rat gastrocnemius muscle under anesthesia, which induced mechanical hyperalgesia 2–4 days after LC. MT (manual compression) ameliorated mechanical hyperalgesia. Then, we used capillary electrophoresis time-of-flight mass spectroscopy (CE-TOFMS) to investigate early effects of MT on the metabolite profiles of the muscle experiencing DOMS. The rats were divided into the following three groups; (1) normal controls, (2) rats with LC application (LC group), and (3) rats undergoing MT after LC (LC + MT group). According to the CE-TOFMS analysis, a total of 171 metabolites were detected among the three groups, and 19 of these metabolites were significant among the groups. Furthermore, the concentrations of eight metabolites, including branched-chain amino acids, carnitine, and malic acid, were significantly different between the LC + MT and LC groups. The results suggest that MT significantly altered metabolite profiles in DOMS. According to our findings and previous data regarding metabolites in mitochondrial metabolism, the ameliorative effects of MT might be mediated partly through alterations in metabolites associated with mitochondrial respiration. PMID:25713324

  6. Low intensity laser therapy accelerates muscle regeneration in aged rats

    PubMed Central

    Vatansever, Fatma; Rodrigues, Natalia C.; Assis, Livia L.; Peviani, Sabrina S.; Durigan, Joao L.; Moreira, Fernando M.A.; Hamblin, Michael R.; Parizotto, Nivaldo A.

    2013-01-01

    Background Elderly people suffer from skeletal muscle disorders that undermine their daily activity and quality of life; some of these problems can be listed as but not limited to: sarcopenia, changes in central and peripheral nervous system, blood hypoperfusion, regenerative changes contributing to atrophy, and muscle weakness. Determination, proliferation and differentiation of satellite cells in the regenerative process are regulated by specific transcription factors, known as myogenic regulatory factors (MRFs). In the elderly, the activation of MRFs is inefficient which hampers the regenerative process. Recent studies found that low intensity laser therapy (LILT) has a stimulatory effect in the muscle regeneration process. However, the effects of this therapy when associated with aging are still unknown. Objective This study aimed to evaluate the effects of LILT (λ=830 nm) on the tibialis anterior (TA) muscle of aged rats. Subjects and methods The total of 56 male Wistar rats formed two population sets: old and young, with 28 animals in each set. Each of these sets were randomly divided into four groups of young rats (3 months of age) with n=7 per group and four groups of aged rats (10 months of age) with n=7 per group. These groups were submitted to cryoinjury + laser irradiation, cryoinjury only, laser irradiation only and the control group (no cryoinjury/no laser irradiation). The laser treatment was performed for 5 consecutive days. The first laser application was done 24 h after the injury (on day 2) and on the seventh day, the TA muscle was dissected and removed under anesthesia. After this the animals were euthanized. Histological analyses with toluidine blue as well as hematoxylin-eosin staining (for counting the blood capillaries) were performed for the lesion areas. In addition, MyoD and VEGF mRNA was assessed by quantitative polymerase chain reaction. Results The results showed significant elevation (p<0.05) in MyoD and VEGF genes expression levels

  7. Temperature-dependent transitions in isometric contractions of rat muscle.

    PubMed Central

    Ranatunga, K W; Wylie, S R

    1983-01-01

    The effect of temperature on tetanic tension development was examined in extensor digitorum longus (fast-twitch) and soleus (slow-twitch) muscles of the rat, in vitro and with direct stimulation. The temperature range was from 35 to 10 degrees C. 2. The maximum tetanic tension decreased slightly on cooling from 35 to 25 degrees C. Cooling below 20 degrees C resulted in a marked depression of tetanic tension. The results were similar in the two muscles. 3. Analysis (in the form of Arrhenius plots) of the rate of tetanic tension development and relaxation clearly showed the occurrence of two phases in their temperature dependence, due to an increased temperature sensitivity below about 25 degrees C. Arrhenius activation energy estimates for temperatures lower than 21 degrees C were around twice as high as those for temperatures higher than 24 degrees C in both muscles. PMID:6887040

  8. Low level laser therapy on injured rat muscle

    NASA Astrophysics Data System (ADS)

    Mantineo, M.; Pinheiro, J. P.; Morgado, A. M.

    2013-06-01

    Although studies show the clinical effectiveness of low level laser therapy (LLLT) in facilitating the muscle healing process, scientific evidence is still required to prove the effectiveness of LLLT and to clarify the cellular and molecular mechanisms triggered by irradiation. Here we evaluate the effect of different LLLT doses, using continuous illumination (830 nm), in the treatment of inflammation induced in the gastrocnemius muscle of Wistar rats, through the quantification of cytokines in systemic blood and histological analysis of muscle tissue. We verified that all applied doses produce an effect on reducing the number of inflammatory cells and the concentration of pro-inflammatory TNF-α and IL-1β cytokines. The best results were obtained for 40 mW. The results may suggest a biphasic dose response curve.

  9. Age effects on rat hindlimb muscle atrophy during suspension unloading

    NASA Technical Reports Server (NTRS)

    Steffen, Joseph M.; Fell, Ronald D.; Geoghegan, Thomas E.; Ringel, Lisa C.; Musacchia, X. J.

    1990-01-01

    The effects of hindlimb unloading on muscle mass and biochemical responses were examined and compared in adult (450-g) and juvenile (200-g) rats after 1, 7, or 14 days of whole-body suspension. Quantitatively and qualitatively the soleus, gastrocnemius, plantaris, and extensor digitorum longus (EDL) muscles of the hindlimb exhibited a differential sensitivity to suspension and weightlessness unloading in both adults and juveniles. The red slow-twitch soleus exhibited the most pronounced atrophy under both conditions, with juvenile responses being greater than adult. In contrast, the fast-twitch EDL hypertrophied during suspension and atrophied during weightlessness, with no significant difference between adults and juveniles. Determination of biochemical parameters (total protein, RNA, and DNA) indicates a less rapid rate of response in adult muscles.

  10. Influence of suspension hypokinesia on rat soleus muscle

    NASA Technical Reports Server (NTRS)

    Templeton, G. H.; Padalino, M.; Manton, J.; Glasberg, M.; Silver, C. J.; Silver, P.; Demartino, G.; Leconey, T.; Klug, G.; Hagler, H.

    1984-01-01

    Hindlimb hypokinesia was induced in rats by the Morey method to characterize the response of the soleus muscle. Rats suspended for 1-4 wk exhibited continuous and significant declines in soleus mass, function, and contractile duration. Soleus speeding was in part explained by an alteration in fiber type. The normal incidence of 70-90 percent type I fibers in the soleus muscle was reduced after 4 wk of suspension to 50 percent or less in 9 of 11 rats. A significant decline in type I myosin isozyme content occurred without a change in that of type II. Other observed histochemical changes were characteristic of denervation. Consistent with soleus atrophy, there was a significant increase in lysosomal (acid) protease activity. One week of recovery after a 2-wk suspension was characterized by a return to values not significantly different from control for muscle wet weights, peak contraction force, one-half relaxation time, and type I myosin. Persistent differences from control were observed in maximal rate of tension development, contraction time, and denervation-like changes.

  11. Quercetin protects rat skeletal muscle from ischemia reperfusion injury.

    PubMed

    Ekinci Akdemir, Fazile Nur; Gülçin, İlhami; Karagöz, Berna; Soslu, Recep

    2016-01-01

    In this study, we investigated the potential beneficial effects of quercetin on skeletal muscle ischemia reperfusion injury. Twenty-four Sprague-Dawley type rats were randomly divided into four groups. In the sham group, only gastrocnemius muscle were removed and given no quercetin. In ischemia group, all the femoral artery, vein and collaterals were occluded in the left hindlimb by applying tourniquate under general anaesthesia for three hours but reperfusion was not done. In the Quercetin + Ischemia reperfusion group, quercetin (200 mg kg(-1) dose orally) was given during one-week reoperation and later ischemia reperfusion model was done. Finally, gastrocnemius muscle samples were removed to measure biochemical parameters. The biomarkers, MDA levels, SOD, CAT and GPx activities, were evaluated related to skeletal muscle ischemia reperfusion injury. MDA levels reduced and SOD, CAT and GPx activities increased significantly in Quercetin + Ischemia reperfusion group. Results clearly showed that Quercetin have a protective role against oxidative damage induced by ischemia reperfusion in rats.

  12. Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats

    NASA Technical Reports Server (NTRS)

    Marsh, D. R.; Criswell, D. S.; Carson, J. A.; Booth, F. W.

    1997-01-01

    Myogenic factor mRNA expression was examined during muscle regeneration after bupivacaine injection in Fischer 344/Brown Norway F1 rats aged 3, 18, and 31 mo of age (young, adult, and old, respectively). Mass of the tibialis anterior muscle in the young rats had recovered to control values by 21 days postbupivacaine injection but in adult and old rats remained 40% less than that of contralateral controls at 21 and 28 days of recovery. During muscle regeneration, myogenin mRNA was significantly increased in muscles of young, adult, and old rats 5 days after bupivacaine injection. Subsequently, myogenin mRNA levels in young rat muscle decreased to postinjection control values by day 21 but did not return to control values in 28-day regenerating muscles of adult and old rats. The expression of MyoD mRNA was also increased in muscles at day 5 of regeneration in young, adult, and old rats, decreased to control levels by day 14 in young and adult rats, and remained elevated in the old rats for 28 days. In summary, either a diminished ability to downregulate myogenin and MyoD mRNAs in regenerating muscle occurs in old rat muscles, or the continuing myogenic effort includes elevated expression of these mRNAs.

  13. Implantation of muscle satellite cells overexpressing myogenin improves denervated muscle atrophy in rats.

    PubMed

    Shen, H; Lv, Y; Shen, X Q; Xu, J H; Lu, H; Fu, L C; Duan, T

    2016-02-01

    This study evaluated the effect of muscle satellite cells (MSCs) overexpressing myogenin (MyoG) on denervated muscle atrophy. Rat MSCs were isolated and transfected with the MyoG-EGFP plasmid vector GV143. MyoG-transfected MSCs (MTMs) were transplanted into rat gastrocnemius muscles at 1 week after surgical denervation. Controls included injections of untransfected MSCs or the vehicle only. Muscles were harvested and analyzed at 2, 4, and 24 weeks post-transplantation. Immunofluorescence confirmed MyoG overexpression in MTMs. The muscle wet weight ratio was significantly reduced at 2 weeks after MTM injection (67.17±6.79) compared with muscles injected with MSCs (58.83±5.31) or the vehicle (53.00±7.67; t=2.37, P=0.04 and t=3.39, P=0.007, respectively). The muscle fiber cross-sectional area was also larger at 2 weeks after MTM injection (2.63×10³±0.39×10³) compared with MSC injection (1.99×10³±0.58×10³) or the vehicle only (1.57×10³±0.47×10³; t=2.24, P=0.049 and t=4.22, P=0.002, respectively). At 4 and 24 weeks post-injection, the muscle mass and fiber cross-sectional area were similar across all three experimental groups. Immunohistochemistry showed that the MTM group had larger MyoG-positive fibers. The MTM group (3.18±1.13) also had higher expression of MyoG mRNA than other groups (1.41±0.65 and 1.03±0.19) at 2 weeks after injection (t=2.72, P=0.04). Transplanted MTMs delayed short-term atrophy of denervated muscles. This approach can be optimized as a novel stand-alone therapy or as a bridge to surgical re-innervation of damaged muscles.

  14. Twitch tension, muscle weight, and fiber area of exercised reinnervating rat skeletal muscle.

    PubMed

    Hie, H B; van Nie, C J; Vermeulen-van der Zee, E

    1982-12-01

    The purpose of this study was to evaluate the effect of dynamic exercise on weight and isometric twitch tension of the reinnervating rat gastrocnemius-plantaris muscle complex as well as on histology of the reinnervating plantaris muscle. Two groups of 6-week-old female Wistar rats, 1 control (n = 17) and 1 experimental (n = 17), were denervated unilaterally by cutting and resecting the sciatic nerve. To effect reinnervation a skin grafting operation was carried out on the nerve so that the gap caused by resection was bridged. The experimental group began exercising on a motor-driven treadmill 18 days following the graft. A progressive training program of 18 weeks of treadmill running, 5 days/week, was carried out by the animals. Training intensity was gradually increased until during the final 3 weeks they were running up a 25% grade at a speed of 720m/hour for 2 hours a day. Exercise did not damage the reinnervating muscle. Absolute wet weight and maximum isometric twitch tension of the reinnervating gastrocnemius-plantaris muscle complex were increased significantly, by 15 1/2% and 30% respectively, after exercise. Training resulted in a significant increase in fiber and muscle cross-sectional areas of the reinnervating plantaris, by 28% and 23% respectively. Exercise brought about no change in total relative amount of connective tissue in the reinnervating plantaris. This study indicates that dynamic exercise has a significant positive effect on the weight, twitch tension and histologic appearance of the reinnervating gastrocnemius-plantaris muscle and thus may enhance their functional recovery. It is likely that this type of training is also effective in the treatment of patients recovering from peripheral nerve injuries.

  15. Immunomodulatory effects of massage on nonperturbed skeletal muscle in rats

    PubMed Central

    Waters-Banker, Christine; Dupont-Versteegden, Esther E.

    2013-01-01

    Massage is an ancient manual therapy widely utilized by individuals seeking relief from various musculoskeletal maladies. Despite its popularity, the majority of evidence associated with massage benefits is anecdotal. Recent investigations have uncovered physiological evidence supporting its beneficial use following muscle injury; however, the effects of massage on healthy, unperturbed skeletal muscle are unknown. Utilizing a custom-fabricated massage mimetic device, the purpose of this investigation was to elucidate the effects of various loading magnitudes on healthy skeletal muscle with particular interest in the gene expression profile and modulation of key immune cells involved in the inflammatory response. Twenty-four male Wistar rats (200 g) were subjected to cyclic compressive loading (CCL) over the right tibialis anterior muscle for 30 min, once a day, for 4 consecutive days using four loading conditions: control (0N), low load (1.4N), moderate load (4.5N), and high load (11N). Microarray analysis showed that genes involved with the immune response were the most significantly affected by application of CCL. Load-dependent changes in cellular abundance were seen in the CCL limb for CD68+ cells, CD163+ cells, and CD43+cells. Surprisingly, load-independent changes were also discovered in the non-CCL contralateral limb, suggesting a systemic response. These results show that massage in the form of CCL exerts an immunomodulatory response to uninjured skeletal muscle, which is dependent upon the applied load. PMID:24201707

  16. Early changes in muscle atrophy and muscle fiber type conversion after spinal cord transection and peripheral nerve transection in rats

    PubMed Central

    2013-01-01

    Background Spinal cord transection and peripheral nerve transection cause muscle atrophy and muscle fiber type conversion. It is still unknown how spinal cord transection and peripheral nerve transection each affect the differentiation of muscle fiber type conversion mechanism and muscle atrophy. The aim of our study was to evaluate the difference of muscle weight change, muscle fiber type conversion, and Peroxisome proliferator-activated receptor-γ coactivatior-1α (PGC-1α) expression brought about by spinal cord transection and by peripheral nerve transection. Methods Twenty-four Wistar rats underwent surgery, the control rats underwent a laminectomy; the spinal cord injury group underwent a spinal cord transection; the denervation group underwent a sciatic nerve transection. The rats were harvested of the soleus muscle and the TA muscle at 0 week, 1 week and 2 weeks after surgery. Histological examination was assessed using hematoxylin and eosin (H&E) staining and immunofluorescent staing. Western blot was performed with 3 groups. Results Both sciatic nerve transection and spinal cord transection caused muscle atrophy with the effect being more severe after sciatic nerve transection. Spinal cord transection caused a reduction in the expression of both sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection produced an increase in expression of sMHC protein and PGC-1α protein in the soleus muscle. The results of the expression of PGC-1α were expected in other words muscle atrophy after sciatic nerve transection is less than after spinal cord transection, however muscle atrophy after sciatic nerve transection was more severe than after spinal cord transection. Conclusion In the conclusion, spinal cord transection diminished the expression of sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection enhanced the expression of sMHC protein and PGC-1α protein in the soleus

  17. 2-D protein maps of rat gastrocnemius and soleus muscles: a tool for muscle plasticity assessment.

    PubMed

    Gelfi, Cecilia; Viganò, Agnese; De Palma, Sara; Ripamonti, Marilena; Begum, Shajna; Cerretelli, Paolo; Wait, Robin

    2006-01-01

    Functional characterization of muscle fibers relies on ATPase activity and on differential measurements of metabolic proteins, including mitochondrial and glycolytic enzymes, glucose, lactate and lactic acid transporters, calcium cycling proteins and components of the contractile machinery. The recent introduction of microarray technology has enabled detailed gene expression studies under different physiological and pathological conditions, thus generating novel hypotheses on muscle function. However, microarray approaches are limited by the incomplete genome coverage of currently available chips, and by poor correlation between mRNA concentration and protein expression level. We have used 2-DE and MS to build a reference map of proteins from rat mixed gastrocnemius and soleus muscle, and to assess qualitative and quantitative differences in protein distribution between these two functionally dissimilar muscles. More than 800 spots on each gel were detected by silver staining, of which 167 were excised, digested in-gel with trypsin and analyzed by ESI-MS/MS. One hundred and twenty eight distinct gene products were identified, including metabolic, transport and contractile proteins. Forty one spots displayed differences in relative expression level between mixed gastrocnemius and soleus samples. These data not only enable differentiation of functionally distinct slow-twitch and fast-twitch fiber types, but also provide tools for investigating muscle plasticity in response to physiological and environmental conditions such as aging or hypoxia.

  18. Effects of acidification and increased extracellular potassium on dynamic muscle contractions in isolated rat muscles.

    PubMed

    Overgaard, Kristian; Højfeldt, Grith Westergaard; Nielsen, Ole Bækgaard

    2010-12-15

    Since accumulation of both H(+) and extracellular K(+) have been implicated in the reduction in dynamic contractile function during intense exercise, we investigated the effects of acidification and high K(+) on muscle power and the force-velocity relation in non-fatigued rat soleus muscles. Contractions were elicited by supramaximal electrical stimulation at 60 Hz. Force-velocity (FV) curves were obtained by fitting data on force and shortening velocity at different loads to the Hill equation. Acidification of the muscles by incubation with up to 24 mm lactic acid produced no significant changes in maximal power (P(max)) at 30 °C. More pronounced acidification, obtained by increasing CO(2) levels in the equilibration gas from 5% to 53%, markedly decreased P(max) and maximal isometric force (F(max)), increased the curvature of the FV relation, but left maximal shortening velocity (V(max)) unchanged. Increase of extracellular K(+) from 4 to 10 mm caused a depression of 58% in P(max) and 52% in F(max), but had no significant effect on V(max) or curvature of the FV curve. When muscles at 10 mM K(+) were acidified by 20 mm lactic acid, P(max) and F(max) recovered completely to the initial control level at 4 mm K(+). CO(2) acidification also induced significant recovery of dynamic contractions, but not entirely to control levels. These results demonstrate that in non-fatigued muscles severe acidification can be detrimental to dynamic contractile function, but in muscles depolarised by exposure to high extracellular [K(+)], approaching the [K(+)] level seen during intense fatiguing exercise, acidification can have positive protective effects on dynamic muscle function.

  19. Toxicity of statins on rat skeletal muscle mitochondria.

    PubMed

    Kaufmann, P; Török, M; Zahno, A; Waldhauser, K M; Brecht, K; Krähenbühl, S

    2006-10-01

    We investigated mitochondrial toxicity of four lipophilic stains (cerivastatin, fluvastatin, atorvastatin, simvastatin) and one hydrophilic statin (pravastatin). In L6 cells (rat skeletal muscle cell line), the four lipophilic statins (100 micromol/l) induced death in 27-49% of the cells. Pravastatin was not toxic up to 1 mmol/l. Cerivastatin, fluvastatin and atorvastatin (100 micromol/l) decreased the mitochondrial membrane potential by 49-65%, whereas simvastatin and pravastatin were less toxic. In isolated rat skeletal muscle mitochondria, all statins, except pravastatin, decreased glutamate-driven state 3 respiration and respiratory control ratio. Beta-oxidation was decreased by 88-96% in the presence of 100 micromol/l of the lipophilic statins, but only at higher concentrations by pravastatin. Mitochondrial swelling, cytochrome c release and DNA fragmentation was induced in L6 cells by the four lipophilic statins, but not by pravastatin. Lipophilic statins impair the function of skeletal muscle mitochondria, whereas the hydrophilic pravastatin is significantly less toxic.

  20. Effects of insulin and exercise on rat hindlimb muscles after simulated microgravity

    NASA Technical Reports Server (NTRS)

    Stump, Craig S.; Balon, Thomas W.; Tipton, Charles M.

    1992-01-01

    The effect of simulated microgravity on the insulin- and exercise-stimulated glucose uptake and metabolism in the hindlimb muscles of rats was investigated using three groups of rats suspended at 45 head-down tilt (SUS) for 14 days: (1) cage control, (2) exercising (treadmill running) control, and (3) rats subjected to suspension followed by exercise (SUS-E). It was found that the suspension of rats with hindlimbs non-weight bearing led to enhanced muscle responses to insulin and exercise, when these stimuli were applied separately. However, the insulin affect appeared to be impaired after exercise for the SUS-E rats, especially for the soleus muscle.

  1. Effects of prolonged voluntary wheel-running on muscle structure and function in rat skeletal muscle.

    PubMed

    Kariya, Fumihiko; Yamauchi, Hideki; Kobayashi, Keizo; Narusawa, Mistuo; Nakahara, Yoshibumi

    2004-06-01

    We examined the effects of prolonged voluntary wheel-running on skeletal muscle functional and/or structural characteristics in rats. Male Sprague-Dawley rats (5 weeks old) were divided into five groups: (1) 15W-SC, sedentary controls housed in normal plastic cages until age 15 weeks; (2) 15W-VE, housed in a voluntary-exercise (running-wheel) device equipped with housing space until age 15 weeks; (3) 35W-SC, housed in normal plastic cages until age 35 weeks; (4) 35W-VE, housed in the voluntary-exercise device until age 35 weeks, and (5) 35W-MVE, housed in normal plastic cages until age 15 weeks, then in the voluntary-exercise device from age 16 weeks to 35 weeks ("middle age"). At the end of each rat's experimental period, the plantaris muscle was dissected from each hindlimb for analysis of the muscle's functional and/or structural characteristics. Total running distance was similar in 15W-VE and 35W-VE, both being significantly greater than in 35-MVE. The percentage of type IIb myosin heavy chain isoform was significantly lower in each VE group than in the corresponding SC group. This shift from type IIb was significantly greater for 35W-VE than for the other VE groups, which were similar to each other. The cross-sectional area of type IIx fibers was significantly greater in 35W-VE than in 35W-SC, but this was not true for 15W-VE versus 15W-SC or for 35W-MVE versus 35W-SC. No significant difference in citrate synthase activity was detected between any VE group and the corresponding SC group. These results suggest that a prolongation of voluntary wheel-running leads to some advantageous enhancements of functional and/or structural characteristics in rat plantaris.

  2. Muscarinic receptor subtypes in human and rat colon smooth muscle.

    PubMed

    Gómez, A; Martos, F; Bellido, I; Marquez, E; Garcia, A J; Pavia, J; Sanchez de la Cuesta, F

    1992-06-09

    Muscarinic receptor subtypes in human and rat colon smooth muscle homogenates were characterized with [3H]N-methylscopolamine ([3H]NMS) by ligand binding studies. [3H]NMS saturation experiments show the existence of a homogeneous population of non-interacting binding sites with similar affinity (KD values of 1.38 +/- 0.20 nM in human colon smooth muscle and 1.48 +/- 0.47 nM in rat colon smooth muscle) and with Hill slopes close to unity in both samples of tissue. However, a significant (P less than 0.01) increase in muscarinic receptor density (Bmax) is found in human colon (29.9 +/- 2.9 fmol/mg protein) compared with rat colon (17.2 +/- 1.5 fmol/mg protein). Inhibition of [3H]NMS binding by non-labelled compounds shows the following order in human colon: atropine greater than AF-DX 116 greater than pirenzepine. Whereas in rat colon the rank order obtained is atropine greater than pirenzepine greater than AF-DX 116. Atropine and pirenzepine bind to a homogeneous population of binding sites, although pirenzepine shows higher affinity to bind to the sites present in rat colon (Ki = 1.08 +/- 0.08 microM) than those in human colon (Ki = 1.74 +/- 0.02 microM) (P less than 0.05). Similarly, IC50 values obtained in AF-DX 116 competition experiments were significantly different (P less than 0.01) in human colon (IC50 = 1.69 +/- 0.37 microM) than in rat colon (IC50 = 3.78 +/- 0.75 microM). Unlike atropine and pirenzepine, the inhibition of [3H]NMS binding by AF-DX 116 did not yield a simple mass-action binding curve (nH less than 1, P less than 0.01) suggesting the presence of more than one subtype of muscarinic receptor in both species. Computer analysis of these curves with a two binding site model suggests the presence of two populations of receptor. The apparent Ki1 value for the high affinity binding site is 0.49 +/- 0.07 microM for human colon smooth muscle and 0.33 +/- 0.05 microM for rat colon smooth muscle. The apparent Ki2 for the low affinity binding site is 8

  3. Characteristics of locomotion, muscle strength, and muscle tissue in regenerating rat skeletal muscles.

    PubMed

    Iwata, Akira; Fuchioka, Satoshi; Hiraoka, Koichi; Masuhara, Mitsuhiko; Kami, Katsuya

    2010-05-01

    Although numerous studies have aimed to elucidate the mechanisms used to repair the structure and function of injured skeletal muscles, it remains unclear how and when movement recovers following damage. We performed a temporal analysis to characterize the changes in movement, muscle function, and muscle structure after muscle injury induced by the drop-mass technique. At each time-point, movement recovery was determined by ankle kinematic analysis of locomotion, and functional recovery was represented by isometric force. As a histological analysis, the cross-sectional area of myotubes was measured to examine structural regeneration. The dorsiflexion angle of the ankle, as assessed by kinematic analysis of locomotion, increased after injury and then returned to control levels by day 14 post-injury. The isometric force returned to normal levels by day 21 post-injury. However, the size of the myotubes did not reach normal levels, even at day 21 post-injury. These results indicate that recovery of locomotion occurs prior to recovery of isometric force and that functional recovery occurs earlier than structural regeneration. Thus, it is suggested that recovery of the movement and function of injured skeletal muscles might be insufficient as markers for estimating the degree of neuromuscular system reconstitution.

  4. Spontaneously tonic smooth muscle has characteristically higher levels of RhoA/ROK compared with the phasic smooth muscle.

    PubMed

    Patel, Chirag A; Rattan, Satish

    2006-11-01

    The internal anal sphincter (IAS) tone is important for the rectoanal continence. The RhoA/Rho kinase (ROK) pathway has been associated with the agonist-induced sustained contraction of the smooth muscle, but its role in the spontaneously tonic smooth muscle is not known. Present studies compared expression of different components of the RhoA/ROK pathway between the IAS (a truly tonic SM), the rectal smooth muscle (RSM) (a mixture of phasic and tonic), and anococcygeus smooth muscle (ASM) (a purely phasic SM) of rat. RT-PCR and Western blot analyses were performed to determine RhoA, ROCK-II, CPI-17, MYPT1, and myosin light-chain 20 (MLC20). Phosphorylated CPI-17 at threonine-38 residue (p(Thr38)-CPI-17), MYPT1 at threonine-696 residue (p(Thr696)-MYPT1), and MLC20 at threonine-18/serine-19 residues (p(Thr18/Ser19)-MLC20) were also determined in the basal state and after pretreatment with the ROK inhibitor Y 27632. In addition, we compared the effect of Y 27632 on the basal isometric tension and ROK activity in the IAS vs. the RSM. Our data show the highest levels of RhoA, ROCK-II, CPI-17, MLC20, and of phospho-MYPT1, -CPI-17, and -MLC20 in the IAS followed by in the RSM and ASM. Conversely, MYPT1 levels were lowest in the IAS and highest in the ASM. In the IAS, Y 27632 caused a concentration-dependent decrease in the basal tone, levels of phospho-MYPT1, -CPI-17, and -MLC20, and ROK activity. We conclude that RhoA/ROK plays a critical role in the basal tone in the IAS by the inhibition of MLC phosphatase via the phosphorylation of MYPT1 and CPI-17.

  5. Altered Muscle Metabolism in Rats After Thermal Injury

    DTIC Science & Technology

    1982-12-01

    by Herndon et a-ketoglutarate. 600 mM L -alanine, 0.18 mM NADH. 1.2 U/ml al." Briefly, this procedure consists of anesthetizing the rat (50 mg lactate...whole homogenates of the gastrocnemius muscle 9 sec and the abdomen for 3 sec in 980C water. Saline (20 ml) was to oxidize pyruvate- l -"C to "CO, was...the same time Econofluor (New England Nuclear, Boston. Mass.) and 10% metha- of day. nol. Oleate- l -’C oxidation rates by whole gastrocnemius homoge

  6. Estimation of pyruvate decarboxylation in perfused rat skeletal muscle.

    PubMed

    Schadewaldt, P; Münch, U; Prengel, M; Staib, W

    1983-10-31

    By the determination of pyruvate dehydrogenase activity in tissue homogenates only limited information is gained on the actual metabolic flux. We therefore determined pyruvate decarboxylation in isolated rat hindlimbs non recirculating perfused with physiological (1-14C)pyruvate levels. On the basis of perfusate pyruvate specific activity a 14CO2 production of 15.8 +/- 0.5 nmol/min per g muscle was measured. However, by this method the actual pyruvate flux through the enzyme complex is underestimated by a factor of 7 due to the intracellular dilution of label.

  7. Direct observations of muscle arterioles and venules following contraction of skeletal muscle fibres in the rat.

    PubMed Central

    Marshall, J M; Tandon, H C

    1984-01-01

    Direct observations have been made of responses of individual arterioles and venules of rat spinotrapezius muscle to contraction of the skeletal muscle fibres. Stimuli of 4-6 V intensity, 0.1 ms duration, delivered via a micro-electrode inserted into the spinotrapezius, evoked contraction of a small bundle of skeletal muscle fibres, followed by vasodilatation which was limited to all those arterioles and venules which crossed or ran alongside activated muscle fibres. Since venules outside the region of contraction, but supplied by dilating arterioles, were not passively distended by the attendant rise in intravascular pressure, it is concluded that both the arterioles and venules dilated actively in response to muscle contraction. All arterioles responded to a single twitch contraction, the terminal arterioles (7-13 micron i.d.) showing the largest increase in diameter. Collecting venules (9-18 micron i.d.) responded to just two twitches in 1 s and larger venules to five twitches in 1 s. When twitch contractions were continuously evoked for 10 s, the responses in individual arterioles and venules were graded with twitch frequency, the fastest and largest response occurring at 6-8 Hz. Tetanic contraction, at 40 Hz for 1 s, produced faster responses in all vessels, a maximum 55% increase from resting internal diameter being attained in only 8 s in some terminal arterioles. In all vessels the responses to tetanic contraction were equal to the maximal dilatation induced by papaverine. These results, in contrast with conclusions drawn from indirect estimates of venous responses, show that venules, like arterioles, dilate actively in response to muscle contraction. Venule dilatation may reduce the rise in capillary hydrostatic pressure, thereby limiting the outward filtration of fluid. PMID:6747856

  8. Electrical stimulation using sine waveform prevents unloading-induced muscle atrophy in the deep calf muscles of rat.

    PubMed

    Tanaka, Minoru; Hirayama, Yusuke; Fujita, Naoto; Fujino, Hidemi

    2014-09-01

    The aim of this study was to compare the effects of electrical stimulation by using rectangular and sine waveforms in the prevention of deep muscle atrophy in rat calf muscles. Rats were randomly divided into the following groups: control, hindlimb unloading (HU), and HU plus electrical stimulation (ES). The animals in the ES group were electrically stimulated using rectangular waveform (RS) on the left calves and sine waveform (SS) on the right calves, twice a day, for 2 weeks during unloading. HU for 2 weeks resulted in a loss of the muscle mass, a decrease in the cross-sectional area of the muscle fibers, and overexpression of ubiquitinated proteins in the gastrocnemius and soleus muscles. In contrast, electrical stimulation with RS attenuated the HU-induced reduction in the cross-sectional area of muscle fibers and the increase of ubiquitinated proteins in the gastrocnemius muscle. However, electrical stimulation with RS failed to prevent muscle atrophy in the deep portion of the gastrocnemius and the soleus muscles. Nevertheless, electrical stimulation with SS attenuated the HU-induced muscle atrophy and the up-regulation of ubiquitinated proteins in both gastrocnemius and soleus muscles. This indicates that SS was more effective in the prevention of deep muscle atrophy than RS. Since the skin muscle layers act like the plates of a capacitor, separated by the subcutaneous adipose layer, the SS can pass through this capacitor more easily than the RS. Hence, SS can prevent the progressive loss of muscle fibers in the deep portion of the calf muscles.

  9. Antioxidant protection of NO-induced relaxations of the mouse anococcygeus against inhibition by superoxide anions, hydroquinone and carboxy-PTIO.

    PubMed

    Lilley, E; Gibson, A

    1996-09-01

    1. The potential protective effect of several antioxidants [Cu/Zn superoxide dismutase (Cu/Zn SOD), ascorbate, reduced glutathione (GSH), and alpha-tocopherol (alpha-TOC)] on relaxations of the mouse anococcygeus muscle to nitric oxide (NO; 15 microM) and, where appropriate, nitrergic field stimulation (10 Hz; 10 s trains) was investigated. 2. The superoxide anion generating drug duroquinone (100 microM) reduced relaxations to exogenous NO by 54 +/- 6%; this inhibition was partially reversed by Cu/Zn SOD (250 u ml-1), and by ascorbate (500 microM). Following inhibition of endogenous Cu/Zn SOD activity with diethyldithiocarbamate (DETCA), duroquinone (50 microM) also reduced relaxations to nitrergic field stimulation (by 53 +/- 6%) and this effect was again reversed by Cu/Zn SOD and by ascorbate. Neither GSH (500 microM) nor alpha-TOC (400 microM) afforded any protection against duroquinone. 3. Xanthine (20 mu ml-1); xanthine oxidase (100 microM) inhibited NO-induced relaxations by 73 +/- 14%, but had no effect on those to nitrergic field stimulation, even after DETCA treatment. The inhibition of exogenous NO was reduced by Cu/Zn SOD (250 u ml-1) and ascorbate (400 microM), but was unaffected by GSH or alpha-TOC (both 400 microM). 4. Hydroquinone (100 microM) also inhibited relaxations to NO (by 52 +/- 10%), but not nitrergic stimulation. In this case, however, the inhibition was reversed by GSH (5-100 microM) and ascorbate (100-400 microM), although Cu/Zn SOD and alpha-TOC were ineffective. 5. 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO, 50 microM) inhibited NO-induced relaxations by 50 +/- 4%, but had no effect on nitrergic responses; the inhibition was reduced by ascorbate (2-200 microM) and alpha-TOC (10-200 microM), but not by Cu/Zn SOD or GSH. 6. Hydroxocobalamin (5-100 microM) inhibited, equally, relaxations to both NO (-logIC40 3.14 +/- 0.33) and nitrergic stimulation (-logIC40 3.17 +/- 0.22). 7. Thus, a number of

  10. Differences in Age-Related Alterations in Muscle Contraction Properties in Rat Tongue and Hindlimb

    ERIC Educational Resources Information Center

    Connor, Nadine P.; Ota, Fumikazu; Nagai, Hiromi; Russell, John A.; Leverson, Glen

    2008-01-01

    Purpose: Because of differences in muscle architecture and biomechanics, the purpose of this study was to determine whether muscle contractile properties of rat hindlimb and tongue were differentially affected by aging. Method: Deep peroneal and hypoglossal nerves were stimulated in 6 young and 7 old Fischer 344-Brown Norway rats to allow…

  11. Oxygen exchange profile in rat muscles of contrasting fibre types

    PubMed Central

    Behnke, Brad J; McDonough, Paul; Padilla, Danielle J; Musch, Timothy I; Poole, David C

    2003-01-01

    To determine whether fibre type affects the O2 exchange characteristics of skeletal muscle at the microcirculatory level we tested the hypothesis that, following the onset of contractions, muscle comprising predominately type I fibres (soleus, Sol, 86 % type I) would, based on demonstrated blood flow responses, exhibit a blunted microvascular PO2 (PO2,m, which is determined by the O2 delivery () to O2 uptake () ratio) profile (assessed via phosphorescence quenching) compared to muscle of primarily type II fibres (peroneal, Per, 84 % type II). PO2,m was measured at rest, and following the rest-contractions (twitch, 1 Hz, 2–4 V for 120 s) transition in Sol (n = 6) and Per (n = 6) muscles of Sprague-Dawley rats. Both muscles exhibited a delay followed by a mono-exponential decrease in PO2,m to the steady state. However, compared with Sol, Per demonstrated (1) a larger change in baseline minus steady state contracting PO2,m (ΔPO2,m) (Per, 13.4 ± 1.7 mmHg; Sol, 8.6 ± 0.9 mmHg, P < 0.05); (2) a faster mean response time (i.e. time delay (TD) plus time constant (τ); Per, 23.8 ± 1.5 s; Sol, 39.6 ± 4.3 s, P < 0.05); and therefore (3) a greater rate of PO2,m decline (ΔPO2,m/τ; Per, 0.92 ± 0.08 mmHg s−1; Sol, 0.42 ± 0.05 mmHg s−1, P < 0.05). These data demonstrate an increased microvascular pressure head of O2 at any given point after the initial time delay for Sol versus Per following the onset of contractions that is probably due to faster dynamics relative to those of . PMID:12692174

  12. Satellite cell activity in muscle regeneration after contusion in rats.

    PubMed

    Srikuea, Ratchakrit; Pholpramool, Chumpol; Kitiyanant, Yindee; Yimlamai, Tossaporn

    2010-11-01

    1. The role of satellite cells in muscle growth during development is well documented, but the involvement of these cells in muscle repair after contusion is less well known. In the present study, we investigated the time-course of satellite cell activity (from 3h to 7days) after contusion of rat gastrocnemius muscle using specific molecular markers for immunofluorescence and real-time polymerase chain reaction (PCR). 2. Inflammation of the injured muscle occurred within 6h, followed by disintegration of the damaged myofibres within 12h. Newly formed myofibres appeared by Day 7. 3. The number of MyoD-positive nuclei (activated satellite cells) in the injured muscle was significantly increased by 6h, reaching a maximum by 12h after contusion. However, the number of MyoD-positive nuclei decreased towards control levels by Day 7. Changes in the number of bromodeoxyuridine-labelled nuclei (proliferating satellite cells) paralleled the changes seen in the number of MyoD-positive nuclei. Conversely, expression of myogenin protein was not apparent until Day 3 and increased further by Day 7. Colabelling of MyoD and myogenin was seen in only a few cells. 4. The time-course of MyoD mRNA expression corresponded with MyoD protein expression. However, there were two peaks in myogenin mRNA expression: 6h and Day 7 after contusion. The second peak coincided with upregulation of myostatin mRNA levels. 5. The results of the present study suggest that contusion activates a homogeneous population of satellite cells to proliferate within 3days, followed by differentiation to form new myofibres. The latter may be regulated, in part, by myostatin.

  13. Regulatory Mechanism of Muscle Disuse Atrophy in Adult Rats

    NASA Technical Reports Server (NTRS)

    1993-01-01

    During the last phase of NAG 2-386 we completed three studies. The effects of 14 days of weightlessness; the vastus medialis (VM) from flight rats in COSMOS 2044 was compared with the VM from tail suspended rats and other controls. The type I and II fibers in the mixed fiber portion of the VM were significantly reduced in flight rats and capillary densities paralleled the fiber density changes. The results of this project compared favorably with those in the extensor digitorum longus following seven days of flight in SL 3. The cardiovascular projects focused on the blood pressure changes in head down tilted rats (HDT) and non-head down tilted (N-HDT) rats. Blood pressures (MAP, SP and DP) were significantly elevated through seven days of HDT and rapidly returned to control levels within one day after removal from the HDT position. The N-HDT showed some slight rise in blood pressure but these were not as great and they were not as rapid. The HDT rats were characterized as exhibiting transient hypertension. These results led to some of the microvascular and vascular graduate student projects of Dr. Bernhard Stepke. Also our results refute or, at least, do not agree with previous reports from other laboratories. Each animal, in our blood pressure projects, served as its own control thereby providing more accurate results. Also, our experiments focused on recovery studies which can, in and of themselves, provide guidelines for flight experiments concerned with blood pressure changes. Another experiment was conducted to examine the role of testicular atrophy in whole body suspended (WBS) and tail suspended (TS) rats. We worked in conjunction with Dr. D.R. Deaver's laboratory at Pennsylvania State University and Dr. R. P. Amann at Colorado State University. In the TS rats the testes are retracted into the abdominal cavity, unless a ligature is placed to maintain them in the external scrotal sac. The cryptorchid condition in TS rats results in atrophy of the testes and

  14. Muscle Fatigue Affects the Interpolated Twitch Technique When Assessed Using Electrically-Induced Contractions in Human and Rat Muscles

    PubMed Central

    Neyroud, Daria; Cheng, Arthur J.; Bourdillon, Nicolas; Kayser, Bengt; Place, Nicolas; Westerblad, Håkan

    2016-01-01

    The interpolated twitch technique (ITT) is the gold standard to assess voluntary activation and central fatigue. Yet, its validity has been questioned. Here we studied how peripheral fatigue can affect the ITT. Repeated contractions at submaximal frequencies were produced by supramaximal electrical stimulations of the human adductor pollicis muscle in vivo and of isolated rat soleus fiber bundles; an extra stimulation pulse was given during contractions to induce a superimposed twitch. Human muscles fatigued by repeated 30-Hz stimulation trains (3 s on–1 s off) showed an ~80% reduction in the superimposed twitch force accompanied by a severely reduced EMG response (M-wave amplitude), which implies action potential failure. Subsequent experiments combined a less intense stimulation protocol (1.5 s on–3 s off) with ischemia to cause muscle fatigue, but which preserved M-wave amplitude. However, the superimposed twitch force still decreased markedly more than the potentiated twitch force; with ITT this would reflect increased “voluntary activation.” In contrast, the superimposed twitch force was relatively spared when a similar protocol was performed in rat soleus bundles. Force relaxation was slowed by >150% in fatigued human muscles, whereas it was unchanged in rat soleus bundles. Accordingly, results similar to those in the human muscle were obtained when relaxation was slowed by cooling the rat soleus muscles. In conclusion, our data demonstrate that muscle fatigue can confound the quantification of central fatigue using the ITT. PMID:27445844

  15. Muscle Fatigue Affects the Interpolated Twitch Technique When Assessed Using Electrically-Induced Contractions in Human and Rat Muscles.

    PubMed

    Neyroud, Daria; Cheng, Arthur J; Bourdillon, Nicolas; Kayser, Bengt; Place, Nicolas; Westerblad, Håkan

    2016-01-01

    The interpolated twitch technique (ITT) is the gold standard to assess voluntary activation and central fatigue. Yet, its validity has been questioned. Here we studied how peripheral fatigue can affect the ITT. Repeated contractions at submaximal frequencies were produced by supramaximal electrical stimulations of the human adductor pollicis muscle in vivo and of isolated rat soleus fiber bundles; an extra stimulation pulse was given during contractions to induce a superimposed twitch. Human muscles fatigued by repeated 30-Hz stimulation trains (3 s on-1 s off) showed an ~80% reduction in the superimposed twitch force accompanied by a severely reduced EMG response (M-wave amplitude), which implies action potential failure. Subsequent experiments combined a less intense stimulation protocol (1.5 s on-3 s off) with ischemia to cause muscle fatigue, but which preserved M-wave amplitude. However, the superimposed twitch force still decreased markedly more than the potentiated twitch force; with ITT this would reflect increased "voluntary activation." In contrast, the superimposed twitch force was relatively spared when a similar protocol was performed in rat soleus bundles. Force relaxation was slowed by >150% in fatigued human muscles, whereas it was unchanged in rat soleus bundles. Accordingly, results similar to those in the human muscle were obtained when relaxation was slowed by cooling the rat soleus muscles. In conclusion, our data demonstrate that muscle fatigue can confound the quantification of central fatigue using the ITT.

  16. Botulinum toxin injection causes hyper-reflexia and increased muscle stiffness of the triceps surae muscle in the rat.

    PubMed

    Pingel, Jessica; Wienecke, Jacob; Lorentzen, Jakob; Nielsen, Jens Bo

    2016-12-01

    Botulinum toxin is used with the intention of diminishing spasticity and reducing the risk of development of contractures. Here, we investigated changes in muscle stiffness caused by reflex activity or elastic muscle properties following botulinum toxin injection in the triceps surae muscle in rats. Forty-four rats received injection of botulinum toxin in the left triceps surae muscle. Control measurements were performed on the noninjected contralateral side in all rats. Acute experiments were performed, 1, 2, 4, and 8 wk following injection. The triceps surae muscle was dissected free, and the Achilles tendon was cut and attached to a muscle puller. The resistance of the muscle to stretches of different amplitudes and velocities was systematically investigated. Reflex-mediated torque was normalized to the maximal muscle force evoked by supramaximal stimulation of the tibial nerve. Botulinum toxin injection caused severe atrophy of the triceps surae muscle at all time points. The force generated by stretch reflex activity was also strongly diminished but not to the same extent as the maximal muscle force at 2 and 4 wk, signifying a relative reflex hyperexcitability. Passive muscle stiffness was unaltered at 1 wk but increased at 2, 4, and 8 wk (P < 0.01). These data demonstrate that botulinum toxin causes a relative increase in reflex stiffness, which is likely caused by compensatory neuroplastic changes. The stiffness of elastic elements in the muscles also increased. The data are not consistent with the ideas that botulinum toxin is an efficient antispastic medication or that it may prevent development of contractures.

  17. Expression of nestin, desmin and vimentin in intact and regenerating muscle spindles of rat hind limb skeletal muscles.

    PubMed

    Cízková, Dana; Soukup, Tomás; Mokrý, Jaroslav

    2009-02-01

    We describe the expression and distribution patterns of nestin, desmin and vimentin in intact and regenerating muscle spindles of the rat hind limb skeletal muscles. Regeneration was induced by intramuscular isotransplantation of extensor digitorum longus (EDL) or soleus muscles from 15-day-old rats into the EDL muscle of adult female inbred Lewis rats. The host muscles with grafts were excised after 7-, 16-, 21- and 29-day survival and immunohistochemically stained. Nestin expression in intact spindles in host muscles was restricted to Schwann cells of sensory and motor nerves. In transplanted muscles, however, nestin expression was also found in regenerating "spindle fibers", 7 and 16 days after grafting. From the 21st day onwards, the regenerated spindle fibers were devoid of nestin immunoreactivity. Desmin was detected in spindle fibers at all developmental stages in regenerating as well as in intact spindles. Vimentin was expressed in cells of the outer and inner capsules of all muscle spindles and in newly formed myoblasts and myotubes of regenerating spindles 7 days after grafting. Our results show that the expression pattern of these intermediate filaments in regenerating spindle fibers corresponds to that found in regenerating extrafusal fibers, which supports our earlier suggestion that they resemble small-diameter extrafusal fibers.

  18. Muscle glucose uptake in the rat after suspension with single hindlimb weight bearing

    NASA Technical Reports Server (NTRS)

    Stump, Craig S.; Woodman, Christopher R.; Fregosi, Ralph F.; Tipton, Charles M.

    1993-01-01

    An examination is conducted of the effect of nonweight-bearing conditions, and the systemic influences of simulated microgravity on rat hindlimb muscles. The results obtained suggest that the increases in hindlimb muscle glucose uptake and extracellular space associated with simulated microgravity persist with hindlimb weightbearing, despite the prevention of muscle atrophy. The mechanism (or mechanisms) responsible for these effects are currently unknown.

  19. [Amino acid composition of the rat quadriceps femoris muscle after a flight on the Kosmos-936 biosatellite].

    PubMed

    Vlasova, T F; Miroshnikova, E B; Poliakov, V V; Murugova, T P

    1982-01-01

    The amino acid composition of the quadriceps muscle of rats flown onboard the biosatellite Cosmos-936 and exposed to the ground-based synchronous control experiment was studied. The weightless rats showed changes in the amino acid concentration in the quadriceps muscle. The centrifuged flight and synchronous rats displayed an accumulation of free amino acids in the above muscle.

  20. The influence of rat suspension-hypokinesia on the gastrocnemius muscle

    NASA Technical Reports Server (NTRS)

    Templeton, G. H.; Padalino, M.; Manton, J.; Leconey, T.; Hagler, H.; Glasberg, M.

    1984-01-01

    Hind-limb hypokinesia was induced in rats by the Morey method to characterize the response of the gastrocnemius muscle. A comparison of rats suspended for 2 weeks with weight, sex, and litter-matched control rats indicate no difference in gastrocnemius wet weight, contraction, or one-half relaxation times, but less contractile function as indicated by lowered dP/dt. Myosin ATPase staining identified uniform Type I (slow-twitch) and II (fast-twitch) atrophy in the muscles from 4 of 10 rats suspended for 2 weeks and 1 of 12 rats suspended for 4 weeks; muscles from three other rats of the 4-week group displayed greater Type I atrophy. Other histochemical changes were characteristic of a neuropathy. These data together with recently acquired soleus data (29) indicate the Morey model, like space flight, evokes greater changes in the Type I or slow twitch fibers of the gastrocnemius and soleus muscles.

  1. Alterations in Skeletal Muscle Microcirculation of Head-Down Tilted Rats

    NASA Technical Reports Server (NTRS)

    Musacchia, X. J.; Stepke, Bernhard; Fleming, John T.; Joshua, Irving G.

    1992-01-01

    In this study we assessed the function of microscopic blood vessels in skeletal muscle (cremaster muscle) for alterations which may contribute to the observed elevation of blood pressure associated with head-down tilted whole body suspension (HDT/WBS), a model of weightlessness. Arteriolar baseline diameters, vasoconstrictor responses to norepinephrine (NE) and vasodilation to nitroprusside (NP) were assessed in control rats, rats suspended for 7 or 14 day HDT/WBS rats, and rats allowed to recover for 1 day after 7 days HDT/WBS. Neither baseline diameters nor ability to dilate were influenced by HDT/WBS. Maximum vasoconstriction to norepinephrine was significantly greater in arterioles of hypertensive 14 day HDT/WBS rats. This first study of the intact microvasculature in skeletal muscle indicates that an elevated contractility of arterioles to norepinephrine in suspended rats, and suggests an elevated peripheral resistance in striated muscle may contribute to the increase in blood pressures among animals subjected to HDT/WBS.

  2. Functional Effects of Hyperthyroidism on Cardiac Papillary Muscle in Rats

    PubMed Central

    Vieira, Fabricio Furtado; Olivoto, Robson Ruiz; da Silva, Priscyla Oliveira; Francisco, Julio Cesar; Fogaça, Rosalvo Tadeu Hochmuller

    2016-01-01

    Background Hyperthyroidism is currently recognized to affect the cardiovascular system, leading to a series of molecular and functional changes. However, little is known about the functional influence of hyperthyroidism in the regulation of cytoplasmic calcium and on the sodium/calcium exchanger (NCX) in the cardiac muscle. Objectives To evaluate the functional changes in papillary muscles isolated from animals with induced hyperthyroidism. Methods We divided 36 Wistar rats into a group of controls and another of animals with hyperthyroidism induced by intraperitoneal T3 injection. We measured in the animals' papillary muscles the maximum contraction force, speed of contraction (+df/dt) and relaxation (-df/dt), contraction and relaxation time, contraction force at different concentrations of extracellular sodium, post-rest potentiation (PRP), and contraction force induced by caffeine. Results In hyperthyroid animals, we observed decreased PRP at all rest times (p < 0.05), increased +df/dt and -df/dt (p < 0.001), low positive inotropic response to decreased concentration of extracellular sodium (p < 0.001), reduction of the maximum force in caffeine-induced contraction (p < 0.003), and decreased total contraction time (p < 0.001). The maximal contraction force did not differ significantly between groups (p = 0.973). Conclusion We hypothesize that the changes observed are likely due to a decrease in calcium content in the sarcoplasmic reticulum, caused by calcium leakage, decreased expression of NCX, and increased expression of a-MHC and SERCA2.

  3. Low-level laser irradiation promotes the recovery of atrophied gastrocnemius skeletal muscle in rats.

    PubMed

    Nakano, Jiro; Kataoka, Hideki; Sakamoto, Jyunya; Origuchi, Tomoki; Okita, Minoru; Yoshimura, Toshiro

    2009-09-01

    Low-level laser (LLL) irradiation promotes proliferation of muscle satellite cells, angiogenesis and expression of growth factors. Satellite cells, angiogenesis and growth factors play important roles in the regeneration of muscle. The objective of this study was to examine the effect of LLL irradiation on rat gastrocnemius muscle recovering from disuse muscle atrophy. Eight-week-old rats were subjected to hindlimb suspension for 2 weeks, after which they were released and recovered. During the recovery period, rats underwent daily LLL irradiation (Ga-Al-As laser; 830 nm; 60 mW; total, 180 s) to the right gastrocnemius muscle through the skin. The untreated left gastrocnemius muscle served as the control. In conjunction with LLL irradiation, 5-bromo-2-deoxyuridine (BrdU) was injected subcutaneously to label the nuclei of proliferating cells. After 2 weeks, myofibre diameters of irradiated muscle increased in comparison with those of untreated muscle, but did not recover back to normal levels. Additionally, in the superficial region of the irradiated muscle, the number of capillaries and fibroblast growth factor levels exhibited significant elevation relative to those of untreated muscle. In the deep region of irradiated muscle, BrdU-positive nuclei of satellite cells and/or myofibres increased significantly relative to those of the untreated muscle. The results of this study suggest that LLL irradiation can promote recovery from disuse muscle atrophy in association with proliferation of satellite cells and angiogenesis.

  4. Leucine-enriched essential amino acids attenuate inflammation in rat muscle and enhance muscle repair after eccentric contraction.

    PubMed

    Kato, Hiroyuki; Miura, Kyoko; Nakano, Sayako; Suzuki, Katsuya; Bannai, Makoto; Inoue, Yoshiko

    2016-09-01

    Eccentric exercise results in prolonged muscle damage that may lead to muscle dysfunction. Although inflammation is essential to recover from muscle damage, excessive inflammation may also induce secondary damage, and should thus be suppressed. In this study, we investigated the effect of leucine-enriched essential amino acids on muscle inflammation and recovery after eccentric contraction. These amino acids are known to stimulate muscle protein synthesis via mammalian target of rapamycin (mTOR), which, is also considered to alleviate inflammation. Five sets of 10 eccentric contractions were induced by electrical stimulation in the tibialis anterior muscle of male SpragueDawley rats (8-9 weeks old) under anesthesia. Animals received a 1 g/kg dose of a mixture containing 40 % leucine and 60 % other essential amino acids or distilled water once a day throughout the experiment. Muscle dysfunction was assessed based on isometric dorsiflexion torque, while inflammation was evaluated by histochemistry. Gene expression of inflammatory cytokines and myogenic regulatory factors was also measured. We found that leucine-enriched essential amino acids restored full muscle function within 14 days, at which point rats treated with distilled water had not fully recovered. Indeed, muscle function was stronger 3 days after eccentric contraction in rats treated with amino acids than in those treated with distilled water. The amino acid mix also alleviated expression of interleukin-6 and impeded infiltration of inflammatory cells into muscle, but did not suppress expression of myogenic regulatory factors. These results suggest that leucine-enriched amino acids accelerate recovery from muscle damage by preventing excessive inflammation.

  5. Potassium, Na+,K+-pumps and fatigue in rat muscle.

    PubMed

    Clausen, Torben; Nielsen, Ole Baekgaard

    2007-10-01

    During contractile activity, skeletal muscles undergo a net loss of cytoplasmic K(+) to the interstitial space. During intense exercise, plasma K(+) in human arterial blood may reach 8 mm, and interstitial K(+) 10-12 mm. This leads to depolarization, loss of excitability and contractile force. However, little is known about the effects of these physiological increases in extracellular K(+) ([K(+)](o)) on contractile endurance. Soleus muscles from 4-week-old rats were mounted on transducers for isometric contractions in Krebs-Ringer bicarbonate buffer containing 4-10 mm K(+), and endurance assessed by recording the rate of force decline during continuous stimulation at 60 Hz. Increasing [K(+)](o) from 4 to 8 or 10 mm and equilibrating the muscles for 40 or 20 min augmented the rate of force decline 2.4-fold and 7.2-fold, respectively (P < 0.001). The marked loss of endurance elicited by exposure to 8 or 10 mm K(+) was alleviated or significantly reduced by stimulating the Na(+),K(+)-pumps by intracellular Na(+) loading, the beta(2)-agonist salbutamol, adrenaline, calcitonin gene related peptide, insulin or repeated excitation. In conclusion, excitation-induced increase in [K(+)](o) is an important cause of high-frequency fatigue, and the Na(+),K(+)-pumps are essential for the maintenance of contractile force in the physiological range of [K(+)](o). Recordings of contractile force during continuous stimulation at 8-10 mm K(+) may be used to analyse the effects of agents or conditions influencing the excitability of working isolated muscles.

  6. Glucose uptake and transport in contracting, perfused rat muscle with different pre-contraction glycogen concentrations.

    PubMed Central

    Hespel, P; Richter, E A

    1990-01-01

    1. Glucose uptake and transport, muscle glycogen, free glucose and glucose-6-phosphate concentrations were studied in perfused resting and contracting rat skeletal muscle with different pre-contraction glycogen concentrations. Rats were pre-conditioned by a combination of swimming exercise and diet, resulting in either low (glycogen-depleted rats), normal (control rats) or high (supercompensated rats) muscle glycogen concentrations at the time their hindlimbs were perfused. 2. Compared with control rats, pre-contraction muscle glycogen concentration was approximately 40% lower in glycogen-depleted rats, whereas it was 40% higher in supercompensated rats. Muscle glycogen break-down correlated positively (r = 0.76; P less than 0.001) with pre-contraction muscle glycogen concentration. 3. Glucose uptake during contractions was approximately 50% higher in glycogen-depleted hindquarters than in control hindquarters; in supercompensated hindquarters it was 30% lower. When rats with similar muscle glycogen concentrations were compared, glucose uptake in hindquarters from rats that had exercised on the preceding day was approximately 20% higher than in hindquarters from rats that had not exercised on the preceding day. 4. Muscle membrane glucose transport, as measured by the rate of accumulation of 14C-3-O-methylglucose in the contracting muscles, was 25% lower in supercompensated than in glycogen-depleted muscles at the onset as well as at the end of the 15 min contraction period. 5. Intracellular concentrations of free glucose and glucose-6-phosphate were higher at rest and during the entire 15-min stimulation period in supercompensated muscles than in glycogen-depleted muscles, and glucose uptake during contractions correlated negatively with free glucose (r = -0.52; P less than 0.01) as well as with glucose-6-phosphate (r = -0.49; P less than 0.01) concentrations. 6. It is concluded that: (a) The rate of glucose uptake in contracting skeletal muscle is dependent on the

  7. Cryotherapy Reduces Inflammatory Response Without Altering Muscle Regeneration Process and Extracellular Matrix Remodeling of Rat Muscle

    PubMed Central

    Vieira Ramos, Gracielle; Pinheiro, Clara Maria; Messa, Sabrina Peviani; Delfino, Gabriel Borges; Marqueti, Rita de Cássia; Salvini, Tania de Fátima; Durigan, Joao Luiz Quagliotti

    2016-01-01

    The application of cryotherapy is widely used in sports medicine today. Cooling could minimize secondary hypoxic injury through the reduction of cellular metabolism and injury area. Conflicting results have also suggested cryotherapy could delay and impair the regeneration process. There are no definitive findings about the effects of cryotherapy on the process of muscle regeneration. The aim of the present study was to evaluate the effects of a clinical-like cryotherapy on inflammation, regeneration and extracellular matrix (ECM) remodeling on the Tibialis anterior (TA) muscle of rats 3, 7 and 14 days post-injury. It was observed that the intermittent application of cryotherapy (three 30-minute sessions, every 2 h) in the first 48 h post-injury decreased inflammatory processes (mRNA levels of TNF-α, NF-κB, TGF-β and MMP-9 and macrophage percentage). Cryotherapy did not alter regeneration markers such as injury area, desmin and Myod expression. Despite regulating Collagen I and III and their growth factors, cryotherapy did not alter collagen deposition. In summary, clinical-like cryotherapy reduces the inflammatory process through the decrease of macrophage infiltration and the accumulation of the inflammatory key markers without influencing muscle injury area and ECM remodeling. PMID:26725948

  8. Cryotherapy Reduces Inflammatory Response Without Altering Muscle Regeneration Process and Extracellular Matrix Remodeling of Rat Muscle.

    PubMed

    Vieira Ramos, Gracielle; Pinheiro, Clara Maria; Messa, Sabrina Peviani; Delfino, Gabriel Borges; Marqueti, Rita de Cássia; Salvini, Tania de Fátima; Durigan, Joao Luiz Quagliotti

    2016-01-04

    The application of cryotherapy is widely used in sports medicine today. Cooling could minimize secondary hypoxic injury through the reduction of cellular metabolism and injury area. Conflicting results have also suggested cryotherapy could delay and impair the regeneration process. There are no definitive findings about the effects of cryotherapy on the process of muscle regeneration. The aim of the present study was to evaluate the effects of a clinical-like cryotherapy on inflammation, regeneration and extracellular matrix (ECM) remodeling on the Tibialis anterior (TA) muscle of rats 3, 7 and 14 days post-injury. It was observed that the intermittent application of cryotherapy (three 30-minute sessions, every 2 h) in the first 48 h post-injury decreased inflammatory processes (mRNA levels of TNF-α, NF-κB, TGF-β and MMP-9 and macrophage percentage). Cryotherapy did not alter regeneration markers such as injury area, desmin and Myod expression. Despite regulating Collagen I and III and their growth factors, cryotherapy did not alter collagen deposition. In summary, clinical-like cryotherapy reduces the inflammatory process through the decrease of macrophage infiltration and the accumulation of the inflammatory key markers without influencing muscle injury area and ECM remodeling.

  9. Lateral transmission of force is impaired in skeletal muscles of dystrophic mice and very old rats.

    PubMed

    Ramaswamy, Krishnan S; Palmer, Mark L; van der Meulen, Jack H; Renoux, Abigail; Kostrominova, Tatiana Y; Michele, Daniel E; Faulkner, John A

    2011-03-01

    The dystrophin–glycoprotein complex (DGC) provides an essential link from the muscle fibre cytoskeleton to the extracellular matrix. In dystrophic humans and mdx mice, mutations in the dystrophin gene disrupt the structure of the DGC causing severe damage to muscle fibres. In frog muscles, transmission of force laterally from an activated fibre to the muscle surface occurs without attenuation, but lateral transmission of force has not been demonstrated in mammalian muscles. A unique ‘yoke' apparatus was developed that attached to the epimysium of muscles midway between the tendons and enabled the measurement of lateral force. We now report that in muscles of young wild-type (WT) mice and rats, compared over a wide range of longitudinal forces, forces transmitted laterally showed little or no decrement. In contrast, for muscles of mdx mice and very old rats, forces transmitted laterally were impaired severely. Muscles of both mdx mice and very old rats showed major reductions in the expression of dystrophin. We conclude that during contractions, forces developed by skeletal muscles of young WT mice and rats are transmitted laterally from fibre to fibre through the DGC without decrement. In contrast, in muscles of dystrophic or very old animals, disruptions in DGC structure and function impair lateral transmission of force causing instability and increased susceptibility of fibres to contraction-induced injury.

  10. Multiple stimulations for muscle-nerve-blood vessel unit in compensatory hypertrophied skeletal muscle of rat surgical ablation model.

    PubMed

    Tamaki, Tetsuro; Uchiyama, Yoshiyasu; Okada, Yoshinori; Tono, Kayoko; Nitta, Masahiro; Hoshi, Akio; Akatsuka, Akira

    2009-07-01

    Tissue inflammation and multiple cellular responses in the compensatory enlarged plantaris (OP Plt) muscle induced by surgical ablation of synergistic muscles (soleus and gastrocnemius) were followed over 10 weeks after surgery. Contralateral surgery was performed in adult Wistar male rats. Cellular responses in muscle fibers, blood vessels and nerve fibers were analyzed by immunohistochemistry and electron microscopy. Severe muscle fiber damage and disappearance of capillaries associated with apparent tissue edema were observed in the peripheral portion of OP Plt muscles during the first week, whereas central portions were relatively preserved. Marked cell activation/proliferation was also mainly observed in peripheral portions. Similarly, activated myogenic cells were seen not only inside but also outside of muscle fibers. The former were likely satellite cells and the latter may be interstitial myogenic cells. One week after surgery, small muscle fibers, small arteries and capillaries and several branched-muscle fibers were evident in the periphery, thus indicating new muscle fiber and blood vessel formation. Proliferating cells were also detected in the nerve bundles in the Schwann cell position. These results indicate that the compensatory stimulated/enlarged muscle is a suitable model for analyzing multiple physiological cellular responses in muscle-nerve-blood vessel units under continuous stretch stimulation.

  11. Inhibitory pathways in the circular muscle of rat jejunum

    PubMed Central

    Vanneste, Gwen; Robberecht, Patrick; Lefebvre, Romain A

    2004-01-01

    Conflicting data have been reported on the contribution of nitric oxide (NO) to inhibitory neurotransmission in rat jejunum. Therefore, the mechanism of relaxation and contribution to inhibitory neurotransmission of NO, adenosine 5′-triphosphate (ATP), vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) was examined in the circular muscle of Wistar–Han rat jejunum. Mucosa-free circular muscle strips were precontracted with methacholine in the presence of guanethidine and exposed to electrical field stimulation (EFS) and exogenous NO, ATP, VIP and PACAP. All stimuli induced reduction of tone and inhibition of phasic motility. Only electrically induced responses were sensitive to tetrodotoxin (3 × 10−6 M). NO (10−6–10−4 M)-induced concentration-dependent relaxations that were inhibited by the soluble guanylyl cyclase inhibitor 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one (ODQ; 10−5 M) and the small conductance Ca2+-activated K+-channel blocker apamin (APA; 3 × 10−8 M). Relaxations elicited by exogenous ATP (10−4–10−3 M) were inhibited by the P2Y purinoceptor antagonist reactive blue 2 (RB2; 3 × 10−4 M), but not by APA and ODQ. The inhibitory responses evoked by 10−7 M VIP and 3 × 10−8 M PACAP were decreased by the selective PAC1 receptor antagonist PACAP6–38 (3 × 10−6 M) and APA. The VPAC2 receptor antagonist PG99-465 (3 × 10−7 M) reduced relaxations caused by VIP, but not those by PACAP, while the VPAC1 receptor antagonist PG97-269 (3 × 10−7 M) had no influence. EFS-induced relaxations were inhibited by the NO-synthase inhibitor Nω-nitro-L-arginine methyl ester (3 × 10−4 M), ODQ and APA, but not by RB2, PG97-269, PG99-465 and PACAP6–38. These results suggest that NO is the main inhibitory neurotransmitter in the circular muscle of Wistar–Han rat jejunum acting through a rise in cyclic guanosine monophosphate levels and activation of small conductance Ca2+-dependent K

  12. Epimuscular myofascial force transmission occurs in the rat between the deep flexor muscles and their antagonistic muscles.

    PubMed

    Yucesoy, Can A; Baan, Guus; Huijing, Peter A

    2010-02-01

    The goal of the present study was to test the hypothesis that epimuscular myofascial force transmission occurs between deep flexor muscles of the rat and their antagonists: previously unstudied mechanical effects of length changes of deep flexors on the anterior crural muscles (i.e., extensor digitorum longus (EDL), as well as tibialis anterior and extensor hallucis longus muscle complex (TA+EHL) and peroneal (PER) muscles were assessed experimentally. These muscles or muscle groups were kept at constant length, whereas, distal length changes were imposed on deep flexor (DF) muscles before performing isometric contractions. Distal forces of all muscle-tendon complexes were measured simultaneously, in addition to EDL proximal force. Distal lengthening of DF caused substantial significant effects on its antagonistic muscles: (1) increase in proximal EDL total force (maximally 19.2%), (2) decrease in distal EDL total (maximally 8.4%) and passive (maximally 49%) forces, (3) variable proximo-distal total force differences indicating net proximally directed epimuscular myofascial loads acting on EDL at lower DF lengths and net distally directed loads at higher DF lengths, (4) decrease in TA+EHL total (maximally 50%) and passive (maximally 66.5%) forces and (5) decrease in PER total force (maximally 51.3%). It is concluded that substantial inter-antagonistic epimuscular myofascial force transmission occurs between deep flexor, anterior crural and peroneal muscles. In the light of our present results and recently reported evidence on inter-antagonistic interaction between anterior crural, peroneal and triceps surae muscles, we concluded that epimuscular myofascial force transmission is capable of causing major effects within the entire lower leg of the rat. Implications of such large scale myofascial force transmission are discussed and expected to be crucial to muscle function in healthy, as well as pathological conditions.

  13. Reduction-oxidation state and protein degradation in skeletal muscles of growing rats

    NASA Technical Reports Server (NTRS)

    Fagan, Julie M.; Tischler, Marc E.

    1986-01-01

    The relationship between the NAD redox state and protein degradation during growth was studied in isolated soleus and extensor digitorum longus muscles of 4- to 14-week-old rats. As muscle size increased with age, protein breakdown slowed and the muscles became progressively more reduced as shown by higher ratios of lactate/pyruvate in incubated and fresh-frozen muscle. Correlations were strong between redox state of protein degradation, and muscle mass, and between redox state and protein degradation. This relationship may be important in the slowing of muscle breakdown that occurs with age.

  14. Stimulation of post-traumatic regeneration of skeletal muscles of old rats after x-ray irradiation

    SciTech Connect

    Bulyakova, N.V.; Popova, M.F.

    1987-09-01

    The authors seek a method of stimulating restorative processes in irradiated muscles of old animals. Rats were used in the experiments. Different series of experiments were performed, including complete transverse section of the gastrocnemius muscle after local x-ray irradiation, and laser therapy of the transversly divided gastrocnemius muscle. Post-traumatic regeneration of the gastrocnemius muscle of old rats is illustrated schematically. The experimental data showed that pulsed laser therapy or grafting of minced unirradiated muscle tissue can largely restore the regenerative capacity of the gastrocnemius muscle of old rats when depressed by x-ray irradiation, but the method of grafting minced unirradiated muscle tissue was more effective.

  15. Leucine-enriched essential amino acids attenuate muscle soreness and improve muscle protein synthesis after eccentric contractions in rats.

    PubMed

    Kato, Hiroyuki; Suzuki, Hiromi; Mimura, Masako; Inoue, Yoshiko; Sugita, Mayu; Suzuki, Katsuya; Kobayashi, Hisamine

    2015-06-01

    Eccentric exercise results in prolonged muscle weakness and muscle soreness, which are typical symptoms of muscle damage. Recovery from muscle damage is related to mammalian target of rapamycin (mTOR) activity. Leucine-enriched essential amino acids (LEAAs) stimulate muscle protein synthesis via activation of the mTOR pathway. Therefore, we investigated the effect of LEAAs on muscle protein synthesis and muscle soreness after eccentric contractions (EC). Male Sprague-Dawley rats (9-11 weeks old) were administered an LEAA solution (AminoL40; containing 40 % leucine and 60 % other essential amino acids) at 1 g/kg body weight or distilled water (control) 30 min before and 10 min after EC. Tibialis anterior (TA) muscle was exposed to 500 EC by electrical stimulation under anesthesia. The fractional synthesis rate (FSR; %/h) in the TA muscle was measured by incorporating L-[ring-(2)H5] phenylalanine into skeletal muscle protein. Muscle soreness was evaluated by the paw withdrawal threshold using the Randal-Selitto test with some modifications from 1 to 3 days after EC. The FSR in the EC-control group (0.147 ± 0.016 %/h) was significantly lower than in the sedentary group (0.188 ± 0.016 %/h, p < 0.05). AminoL40 administration significantly mitigated the EC-induced impairment of the FSR (0.172 ± 0.018 %/h). EC decreased the paw withdrawal threshold at 1 and 2 days after EC, which indicated that EC induced muscle soreness. Furthermore, AminoL40 administration alleviated the decreased paw withdrawal threshold. These findings suggest that LEAA supplementation improves the rate of muscle protein synthesis and ameliorates muscle soreness after eccentric exercise.

  16. Muscle-specific changes in length-force characteristics of the calf muscles in the spastic Han-Wistar rat.

    PubMed

    Olesen, Annesofie T; Jensen, Bente R; Uhlendorf, Toni L; Cohen, Randy W; Baan, Guus C; Maas, Huub

    2014-11-01

    The purpose of the present study was to investigate muscle mechanical properties and mechanical interaction between muscles in the lower hindlimb of the spastic mutant rat. Length-force characteristics of gastrocnemius (GA), soleus (SO), and plantaris (PL) were assessed in anesthetized spastic and normally developed Han-Wistar rats. In addition, the extent of epimuscular myofascial force transmission between synergistic GA, SO, and PL, as well as between the calf muscles and antagonistic tibialis anterior (TA), was investigated. Active length-force curves of spastic GA and PL were narrower with a reduced maximal active force. In contrast, active length-force characteristics of spastic SO were similar to those of controls. In reference position (90° ankle and knee angle), higher resistance to ankle dorsiflexion and increased passive stiffness was found for the spastic calf muscle group. At optimum length, passive stiffness and passive force of spastic GA were decreased, whereas those of spastic SO were increased. No mechanical interaction between the calf muscles and TA was found. As GA was lengthened, force from SO and PL declined despite a constant muscle-tendon unit length of SO and PL. However, the extent of this interaction was not different in spastic rats. In conclusion, the effects of spasticity on length-force characteristics were muscle specific. The changes observed for GA and PL muscles are consistent with the changes in limb mechanics reported for human patients. Our results indicate that altered mechanics in spastic rats cannot be attributed to differences in mechanical interaction, but originate from individual muscular structures.

  17. Evidence for increased peroxidative activity in muscles from streptozotocin-diabetic rats

    SciTech Connect

    Lammi-Keefe, C.J.; Swan, P.B.; Hegarty, P.V.J.

    1984-05-01

    The ability of cardiac and skeletal muscles from diabetic rats to metabolize superoxide and hydrogen peroxide was determined by the activities of superoxide dismutase (SOD) and catalase, respectively. Male and female Sprague-Dawley rats, 43 days old, were made diabetic with a single intravenous injection of streptozotocin (70 mg/kg body weight). On the 80th day after injection the blood glucose concentration of these rats was increased fourfold, and the plasma insulin concentration was decreased four- to fivefold compared to controls. Body weights of male diabetic rats were 61% and those of female diabetic rats were 66% of their ad libitum-fed controls. The seven different skeletal muscles examined weighed less in the diabetic rats than in controls of the same age and body weight. Comparison to the body weight controls allowed the distinction of specific effects due to lack of insulin from effects due to retardation in muscle growth. Increased catalase activity in all muscles examined from diabetic rats (plantaris, gastrocnemius, and heart) suggested a response in catalase activity similar to that of starved rats. SOD activity was not altered in the diabetic rat skeletal muscles and erythrocytes, but was somewhat decreased in the heart.

  18. Ontogenetic, gravity-dependent development of rat soleus muscle

    NASA Technical Reports Server (NTRS)

    Ohira, Y.; Tanaka, T.; Yoshinaga, T.; Kawano, F.; Nomura, T.; Nonaka, I.; Allen, D. L.; Roy, R. R.; Edgerton, V. R.

    2001-01-01

    We tested the hypothesis that rat soleus muscle fiber growth and changes in myosin phenotype during the postnatal, preweaning period would be largely independent of weight bearing. The hindlimbs of one group of pups were unloaded intermittently from postnatal day 4 to day 21: the pups were isolated from the dam for 5 h during unloading and returned for nursing for 1 h. Control pups were either maintained with the dam as normal or put on an alternating feeding schedule as described above. The enlargement of mass (approximately 3 times), increase in myonuclear number (approximately 1.6 times) and myonuclear domain (approximately 2.6 times), and transformation toward a slow fiber phenotype (from 56 to 70% fibers expressing type I myosin heavy chain) observed in controls were inhibited by hindlimb unloading. These properties were normalized to control levels or higher within 1 mo of reambulation beginning immediately after the unloading period. Therefore, chronic unloading essentially stopped the ontogenetic developmental processes of 1) net increase in DNA available for transcription, 2) increase in amount of cytoplasm sustained by that DNA pool, and 3) normal transition of myosin isoforms that occur in some fibers from birth to weaning. It is concluded that normal ontogenetic development of a postural muscle is highly dependent on the gravitational environment even during the early postnatal period, when full weight-bearing activity is not routine.

  19. Insulin effect on amino acid uptake by unloaded rat hindlimb muscles

    NASA Technical Reports Server (NTRS)

    Jaspers, S. R.; Tischler, M. E.

    1988-01-01

    The effect of insulin on the uptake of alpha-amino-isobutyric acid (AIB) by unloaded rat hindlimb muscles was investigated using soleus and extensor digitorum longus (EDL) muscles from intact and adrenalectomized (ADX) rats that were tail-casted for six days. It was found that, at insulin levels above 0.00001 units/ml, the in vitro rate of AIB uptake by muscles from intact animals was stimulated more in the weight bearing muscles than in unloaded ones. In ADX animals, this differential response to insulin was abolished.

  20. Changes in antioxidant enzymes and lipid peroxidation in extensor digitorum longus muscles of streptozotocin-diabetic rats may contribute to muscle atrophy.

    PubMed

    Nonaka, Koji; Une, S; Tatsuta, N; Ito, K; Akiyama, J

    2014-12-01

    We investigated muscle atrophy, major antioxidant enzymes and lipid peroxidation in the extensor digitorum longus (EDL, predominantly fast fibers) and soleus (predominantly slow fibers) muscle of streptozotocin-diabetic rats. Female Wistar rats were divided into a control (n = 5) and streptozotocin-induced diabetic group (n = 5). Eight weeks after diabetes induction the EDL and soleus muscles were removed and catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase activity (SOD), and thiobarbituric acid reactive substances (TBARS) levels measured. The CAT activity increased in both the EDL and soleus muscles of the diabetic rats (p < 0.01), whereas the GPX and SOD activities were increased only in the EDL muscle (p < 0.01 and p < 0.05). The TBARS levels were only increased in the EDL muscle of the diabetic rats (p < 0.01). Both muscles showed significant atrophy but the EDL muscle elicited the greatest atrophy. In conclusion, it appears that adaptive responses to oxidative stress were adequate in the soleus muscle, but not in the EDL muscle, of diabetic rats. Thus fast twitch muscle fibers may be more susceptible to oxidative stress than slow twitch muscle fibers and this may contribute to muscle atrophy under diabetic conditions.

  1. Contractile function and energy metabolism of skeletal muscle in rats with secondary carnitine deficiency.

    PubMed

    Roberts, Paul A; Bouitbir, Jamal; Bonifacio, Annalisa; Singh, François; Kaufmann, Priska; Urwyler, Albert; Krähenbühl, Stephan

    2015-08-01

    The consequences of carnitine depletion upon metabolic and contractile characteristics of skeletal muscle remain largely unexplored. Therefore, we investigated the effect of N-trimethyl-hydrazine-3-propionate (THP) administration, a carnitine analog inhibiting carnitine biosynthesis and renal reabsorption of carnitine, on skeletal muscle function and energy metabolism. Male Sprague-Dawley rats were fed a standard rat chow in the absence (CON; n = 8) or presence of THP (n = 8) for 3 wk. Following treatment, rats were fasted for 24 h prior to excision of their soleus and EDL muscles for biochemical characterization at rest and following 5 min of contraction in vitro. THP treatment reduced the carnitine pool by ∼80% in both soleus and EDL muscles compared with CON. Carnitine depletion was associated with a 30% decrease soleus muscle weight, whereas contractile function (expressed per gram of muscle), free coenzyme A, and water content remained unaltered from CON. Muscle fiber distribution and fiber area remained unaffected, whereas markers of apoptosis were increased in soleus muscle of THP-treated rats. In EDL muscle, carnitine depletion was associated with reduced free coenzyme A availability (-25%, P < 0.05), impaired peak tension development (-44%, P < 0.05), and increased glycogen hydrolysis (52%, P < 0.05) during muscle contraction, whereas PDC activation, muscle weight, and water content remained unaltered from CON. In conclusion, myopathy associated with carnitine deficiency can have different causes. Although muscle atrophy, most likely due to increased apoptosis, is predominant in muscle composed predominantly of type I fibers (soleus), disturbance of energy metabolism appears to be the major cause in muscle composed of type II fibers (EDL).

  2. Distinct muscle apoptotic pathways are activated in muscles with different fiber types a rat model of critical illness myopathy

    PubMed Central

    Barnes, Benjamin T.; Confides, Amy L.; Rich, Mark M.; Dupont-Versteegden, Esther E.

    2015-01-01

    Critical illness myopathy (CIM) is associated with severe muscle atrophy and fatigue in affected patients. Apoptotic signaling is involved in atrophy and is elevated in muscles from patients with CIM. In this study we investigated underlying mechanisms of apoptosis-related pathways in muscles with different fiber type composition in a rat model of CIM using denervation and glucocorticoid administration (denervation and steroid-induced myopathy, DSIM). Soleus and tibialis anterior (TA) muscles showed severe muscle atrophy (40–60% of control muscle weight) and significant apoptosis in interstitial as well as myofiber nuclei that was similar between the two muscles with DSIM. Caspase-3 and −8 activities, but not caspase-9 and −12, were elevated in TA and not in soleus muscle, while the caspase-independent proteins endonuclease G (EndoG) and apoptosis inducing factor (AIF) were not changed in abundance nor differentially localized in either muscle. Anti-apoptotic proteins HSP70, −27, and apoptosis repressor with a caspase recruitment domain (ARC) were elevated in soleus compared to TA muscle and ARC was significantly decreased with induction of DSIM in soleus. Results indicate that apoptosis is a significant process associated with DSIM in both soleus and TA muscles, and that apoptosis-associated processes are differentially regulated in muscles of different function and fiber type undergoing atrophy due to DSIM. We conclude that interventions combating apoptosis with CIM may need to be directed towards inhibiting caspase-dependent as well as -independent mechanisms to be able to affect muscles of all fiber types. PMID:25740800

  3. Distinct muscle apoptotic pathways are activated in muscles with different fiber types in a rat model of critical illness myopathy.

    PubMed

    Barnes, Benjamin T; Confides, Amy L; Rich, Mark M; Dupont-Versteegden, Esther E

    2015-06-01

    Critical illness myopathy (CIM) is associated with severe muscle atrophy and fatigue in affected patients. Apoptotic signaling is involved in atrophy and is elevated in muscles from patients with CIM. In this study we investigated underlying mechanisms of apoptosis-related pathways in muscles with different fiber type composition in a rat model of CIM using denervation and glucocorticoid administration (denervation and steroid-induced myopathy, DSIM). Soleus and tibialis anterior (TA) muscles showed severe muscle atrophy (40-60% of control muscle weight) and significant apoptosis in interstitial as well as myofiber nuclei that was similar between the two muscles with DSIM. Caspase-3 and -8 activities, but not caspase-9 and -12, were elevated in TA and not in soleus muscle, while the caspase-independent proteins endonuclease G (EndoG) and apoptosis inducing factor (AIF) were not changed in abundance nor differentially localized in either muscle. Anti-apoptotic proteins HSP70, -27, and apoptosis repressor with a caspase recruitment domain (ARC) were elevated in soleus compared to TA muscle and ARC was significantly decreased with induction of DSIM in soleus. Results indicate that apoptosis is a significant process associated with DSIM in both soleus and TA muscles, and that apoptosis-associated processes are differentially regulated in muscles of different function and fiber type undergoing atrophy due to DSIM. We conclude that interventions combating apoptosis with CIM may need to be directed towards inhibiting caspase-dependent as well as -independent mechanisms to be able to affect muscles of all fiber types.

  4. Volitional Weight-Lifting in Rats Promotes Adaptation via Performance and Muscle Morphology prior to Gains in Muscle Mass

    PubMed Central

    Rader, Erik P; Miller, G Roger; Chetlin, Robert D; Wirth, Oliver; Baker, Brent A

    2014-01-01

    Investigation of volitional animal models of resistance training has been instrumental in our understanding of adaptive training. However, these studies have lacked reactive force measurements, a precise performance measure, and morphological analysis at a distinct phase of training – when initial strength gains precede muscle hypertrophy. Our aim was to expose rats to one month of training (70 or 700 g load) on a custom-designed weight-lifting apparatus for analysis of reactive forces and muscle morphology prior to muscle hypertrophy. Exclusively following 700 g load training, forces increased by 21% whereas muscle masses remained unaltered. For soleus (SOL) and tibialis anterior (TA) muscles, 700 g load training increased muscle fiber number per unit area by ∼20% and decreased muscle fiber area by ∼20%. Additionally, number of muscle fibers per section increased by 18% for SOL muscles. These results establish that distinct morphological alterations accompany early strength gains in a volitional animal model of load-dependent adaptive resistance training. PMID:25392697

  5. The comparative effects of aminoglycoside antibiotics and muscle relaxants on electrical field stimulation response in rat bladder smooth muscle.

    PubMed

    Min, Chang Ho; Min, Young Sil; Lee, Sang Joon; Sohn, Uy Dong

    2016-06-01

    It has been reported that several aminoglycoside antibiotics have a potential of prolonging the action of non-depolarizing muscle relaxants by drug interactions acting pre-synaptically to inhibit acetylcholine release, but antibiotics itself also have a strong effect on relaxing the smooth muscle. In this study, four antibiotics of aminoglycosides such as gentamicin, streptomycin, kanamycin and neomycin were compared with skeletal muscle relaxants baclofen, tubocurarine, pancuronium and succinylcholine, and a smooth muscle relaxant, papaverine. The muscle strips isolated from the rat bladder were stimulated with pulse trains of 40 V in amplitude and 10 s in duration, with pulse duration of 1 ms at the frequency of 1-8 Hz, at 1, 2, 4, 6, 8 Hz respectively. To test the effect of four antibiotics on bladder smooth muscle relaxation, each of them was treated cumulatively from 1 μM to 0.1 mM with an interval of 5 min. Among the four antibiotics, gentamicin and neomycin inhibited the EFS response. The skeletal muscle relaxants (baclofen, tubocurarine, pancuronium and succinylcholine) and inhibitory neurotransmitters (GABA and glycine) did not show any significant effect. However, papaverine, had a significant effect in the relaxation of the smooth muscle. It was suggested that the aminoglycoside antibiotics have inhibitory effect on the bladder smooth muscle.

  6. Muscle fatigue examined at different temperatures in experiments on intact mammalian (rat) muscle fibers

    PubMed Central

    Roots, H.; Ball, G.; Talbot-Ponsonby, J.; King, M.; McBeath, K.; Ranatunga, K. W.

    2009-01-01

    In experiments on small bundles of intact fibers from a rat fast muscle, in vitro, we examined the decline in force in repeated tetanic contractions; the aim was to characterize the effect of shortening and of temperature on the initial phase of muscle fatigue. Short tetanic contractions were elicited at a control repetition rate of 1/60 s, and fatigue was induced by raising the rate to 1/5 s for 2–3 min, both in isometric mode (no shortening) and in shortening mode, in which each tetanic contraction included a ramp shortening at a standard velocity. In experiments at 20°C (n = 12), the force decline during a fatigue run was 25% in the isometric mode but was significantly higher (35%) in the shortening mode. In experiments at different temperatures (10–30°C, n = 11), the tetanic frequency and duration were adjusted as appropriate, and for shortening mode, the velocity was adjusted for maximum power output. In isometric mode, fatigue of force was significantly less at 30°C (∼20%) than at 10°C (∼30%); the power output (force × velocity) was >10× higher at 30°C than at 10°C, and power decline during a fatigue run was less at 30°C (∼20–30%) than at 10°C (∼50%). The finding that the extent of fatigue is increased with shortening contractions and is lower at higher temperatures is consistent with the view that force depression by inorganic phosphate, which accumulates within fibers during activity, may be a primary cause of initial muscle fatigue. PMID:19057001

  7. A New Surgical Model of Skeletal Muscle Injuries in Rats Reproduces Human Sports Lesions.

    PubMed

    Contreras-Muñoz, P; Fernández-Martín, A; Torrella, R; Serres, X; De la Varga, M; Viscor, G; Järvinen, T A H; Martínez-Ibáñez, V; Peiró, J L; Rodas, G; Marotta, M

    2016-03-01

    Skeletal muscle injuries are the most common sports-related injuries in sports medicine. In this work, we have generated a new surgically-induced skeletal muscle injury in rats, by using a biopsy needle, which could be easily reproduced and highly mimics skeletal muscle lesions detected in human athletes. By means of histology, immunofluorescence and MRI imaging, we corroborated that our model reproduced the necrosis, inflammation and regeneration processes observed in dystrophic mdx-mice, a model of spontaneous muscle injury, and realistically mimicked the muscle lesions observed in professional athletes. Surgically-injured rat skeletal muscles demonstrated the longitudinal process of muscle regeneration and fibrogenesis as stated by Myosin Heavy Chain developmental (MHCd) and collagen-I protein expression. MRI imaging analysis demonstrated that our muscle injury model reproduces the grade I-II type lesions detected in professional soccer players, including edema around the central tendon and the typically high signal feather shape along muscle fibers. A significant reduction of 30% in maximum tetanus force was also registered after 2 weeks of muscle injury. This new model represents an excellent approach to the study of the mechanisms of muscle injury and repair, and could open new avenues for developing innovative therapeutic approaches to skeletal muscle regeneration in sports medicine.

  8. Skeletal muscle response to spaceflight, whole body suspension, and recovery in rats

    NASA Technical Reports Server (NTRS)

    Musacchia, X. J.; Steffen, J. M.; Fell, R. D.; Dombrowski, M. J.

    1990-01-01

    The effects of a 7-day spaceflight (SF), 7- and 14-day-long whole body suspension (WBS), and 7-day-long recovery on the muscle weight and the morphology of the soleus and the extensor digitorum longus (EDL) of rats were investigated. It was found that the effect of 7-day-long SF and WBS were highly comparable for both the soleus and the EDL, although the soleus muscle from SF rats showed greater cross-sectional area reduction than that from WBS rats. With a longer duration of WBS, there was a continued reduction in cross-sectional fast-twitch fiber area. Muscle plasticity, in terms of fiber and capillary responses, showed differences in responses of the two types of muscles, indicating that antigravity posture muscles are highly susceptible to unloading.

  9. Effect of seven days of spaceflight on hindlimb muscle protein, RNA and DNA in adult rats

    NASA Technical Reports Server (NTRS)

    Steffen, J. M.; Musacchia, X. J.

    1985-01-01

    Effects of seven days of spaceflight on skeletal muscle (soleus, gastrocnemius, EDL) content of protein, RNA and DNA were determined in adult rats. Whereas total protein contents were reduced in parallel with muscle weights, myofibrillar protein appeared to be more affected. There were no significant changes in absolute DNA contents, but a significant (P less than 0.05) increase in DNA concentration (microgram/milligram) in soleus muscles from flight rats. Absolute RNA contents were significantly (P less than 0.025) decreased in the soleus and gastrocnemius muscles of flight rats, with RNA concentrations reduced 15-30 percent. These results agree with previous ground-based observations on the suspended rat with unloaded hindlimbs and support continued use of this model.

  10. Changes of contractile responses due to simulated weightlessness in rat soleus muscle

    NASA Astrophysics Data System (ADS)

    Elkhammari, A.; Noireaud, J.; Léoty, C.

    1994-08-01

    Some contractile and electrophysiological properties of muscle fibers isolated from the slow-twitch soleus (SOL) and fast-twitch extensor digitorum longus (EDL) muscles of rats were compared with those measured in SOL muscles from suspended rats. In suspendede SOL (21 days of tail-suspension) membrane potential (Em), intracellular sodium activity (aiNa) and the slope of the relationship between Em and log [K]o were typical of fast-twitch muscles. The relation between the maximal amplitude of K-contractures vs Em was steeper for control SOL than for EDL and suspended SOL muscles. After suspension, in SOL muscles the contractile threshold and the inactivation curves for K-contractures were shifted to more positive Em. Repriming of K-contractures was unaffected by suspencion. The exposure of isolated fibers to perchlorate (ClO4-)-containing (6-40 mM) solutions resulted ina similar concentration-dependent shift to more negative Em of activation curves for EDL and suspended SOL muscles. On exposure to a Na-free TEA solution, SOL from control and suspended rats, in contrast to EDL muscles, generated slow contractile responses. Suspended SOL showed a reduced sensitivity to the contracture-producing effect of caffeine compared to control muscles. These results suggested that the modification observed due to suspension could be encounted by changes in the characteristics of muscle fibers from slow to fast-twitch type.

  11. Fatigue and contraction of slow and fast muscles in hypokinetic/hypodynamic rats

    NASA Technical Reports Server (NTRS)

    Fell, R. D.; Gladden, L. B.; Steffen, J. M.; Musacchia, X. J.

    1985-01-01

    The effects of hypokinesia/hypodynamia (H/H) on the fatigability and contractile properties of the rat soleus (S) and gastrocnemius (G) muscles have been investigated experimentally. Whole body suspension for one week was used to induce H/H, and fatigue was brought on by train stimulation for periods of 45 and 16 minutes. Following stimulation, rapid rates of fatigue were observed in the G-muscles of the suspended rats, while minimal fatigue was observed in the S-muscles. The twitch and tetanic contractile properties of the muscles were measured before and after train stimulation. It is found that H/H suspension increased twitch tension in the G-muscles, but did not change any contractile properties in the S-muscles. The peak twitch, train, tetanic tensions and time to peak were unchanged in the S-muscles of the suspended rats. On the basis of the experimental results, it is concluded that 1 wk of muscle atropy induced by H/H significantly increases fatigability in G-muscles, but does not affect the contractile properties of fast-twitch and slow-twitch muscles.

  12. Green tea extract attenuates muscle loss and improves muscle function during disuse, but fails to improve muscle recovery following unloading in aged rats.

    PubMed

    Alway, Stephen E; Bennett, Brian T; Wilson, Joseph C; Sperringer, Justin; Mohamed, Junaith S; Edens, Neile K; Pereira, Suzette L

    2015-02-01

    In this study we tested the hypothesis that green tea extract (GTE) would improve muscle recovery after reloading following disuse. Aged (32 mo) Fischer 344 Brown Norway rats were randomly assigned to receive either 14 days of hindlimb suspension (HLS) or 14 days of HLS followed by normal ambulatory function for 14 days (recovery). Additional animals served as cage controls. The rats were given GTE (50 mg/kg body wt) or water (vehicle) by gavage 7 days before and throughout the experimental periods. Compared with vehicle treatment, GTE significantly attenuated the loss of hindlimb plantaris muscle mass (-24.8% vs. -10.7%, P < 0.05) and tetanic force (-43.7% vs. -25.9%, P <0.05) during HLS. Although GTE failed to further improve recovery of muscle function or mass compared with vehicle treatment, animals given green tea via gavage maintained the lower losses of muscle mass that were found during HLS (-25.2% vs. -16.0%, P < 0.05) and force (-45.7 vs. -34.4%, P < 0.05) after the reloading periods. In addition, compared with vehicle treatment, GTE attenuated muscle fiber cross-sectional area loss in both plantaris (-39.9% vs. -23.9%, P < 0.05) and soleus (-37.2% vs. -17.6%) muscles after HLS. This green tea-induced difference was not transient but was maintained over the reloading period for plantaris (-45.6% vs. -21.5%, P <0.05) and soleus muscle fiber cross-sectional area (-38.7% vs. -10.9%, P <0.05). GTE increased satellite cell proliferation and differentiation in plantaris and soleus muscles during recovery from HLS compared with vehicle-treated muscles and decreased oxidative stress and abundance of the Bcl-2-associated X protein (Bax), yet this did not further improve muscle recovery in reloaded muscles. These data suggest that muscle recovery following disuse in aging is complex. Although satellite cell proliferation and differentiation are critical for muscle repair to occur, green tea-induced changes in satellite cell number is by itself insufficient to

  13. Gated /sup 31/P NMR study of tetanic contraction in rat muscle depleted of phosphocreatine

    SciTech Connect

    Shoubridge, E.A.; Radda, G.K.

    1987-05-01

    Rats were fed a diet containing 1% ..beta..-guanidino-propionic acid (GPA) for 6-12 wk to deplete their muscles of phosphocreatine (PCr). Gated /sup 31/P nuclear magnetic resonance (NMR) spectra were obtained from the gastrocnemius-plantaris muscle at various time points during either a 1- or 3-s isometric tetanic contraction using a surface coil. The energy cost of a 1-s tetanus in unfatigued control rat muscle was 48.4 ..mu..mol ATP x g dry wt/sup -1/ x s/sup -1/ and was largely supplied by PCr; anaerobic glycogenolysis was negligible. In GPA-fed rats PCr was undetectable after 400 ms. This had no effect on initial force generated per gram, which was not significantly different from controls. Developed tension in a 3-s tetanus in GPA-fed rats could be divided into a peak phase (duration 0.8-0.9 s) and a plateau phase (65% peak tension) in which PCr was undetectable and the (ATP) was < 20% of that in control muscle. Energy from glycogenolysis was sufficient to maintain force generation at this submaximal level. Mean net glycogen utilization per 3-s tetanus was 78% greater than in control muscle. However, the observed decrease in intracellular pH was less than that expected from energy budget calculations, suggesting either increased buffering capacity or modulation of ATP hydrolysis in the muscles of GPA-fed rats. The results demonstrate that the transport role of PCr is not essential in contracting muscle in GPA-fed rats. PCr is probably important in this regard in the larger fibers of control muscle. Although fast-twitch muscles depleted of PCr have nearly twice the glycogen reserves of control muscle, glycogenolysis is limited in its capacity to fill the role of PCr as an energy buffer under conditions of maximum ATP turnover.

  14. Effects of hypokinesia and hypodynamia upon protein turnover in hindlimb muscles of the rat

    NASA Technical Reports Server (NTRS)

    Loughna, Paul T.; Goldspink, David F.; Goldspink, Geoffrey

    1987-01-01

    Hypokinesia/hypodynamia was induced in the hindlimb muscles of the rat, using a suspension technique. This caused differing degrees of atrophy in different muscles. However, this atrophy was reduced in muscles held in a lenghthened position. The greatest degree of wasting was observed in the unstretched soleus, a slow postural muscle, where both Type 1 and Type 2a fibers atrophied to the same degree. However, wasting of the gastrocnemius muscle was associated with a reduction in the size of the Type 2b fibers. In both slow-postural and fast-phasic hindlimb muscles, atrophy was brought about by a reduction in the rate of protein synthesis in conjunction with an elevation in the rate of protein degradation. When inactive muscles were passively stretched, both protein synthesis and degradation were dramatically elevated. Even periods of stretch of as little as 0.5 h/d were found to significantly decrease atrophy in inactive muscles.

  15. Effect of collagen digestion on the passive elastic properties of diaphragm muscle in rat.

    PubMed

    Rowe, Justin; Chen, Qingshan; Domire, Zachary J; McCullough, Matthew B; Sieck, Gary; Zhan, Wen-Zhi; An, Kai-Nan

    2010-01-01

    Effects of collagen digestion have been defined up to the fibril level. However, the question remains as to whether the alteration of skeletal muscle extracellular matrix (ECM) affects a muscle's passive elastic response. Various elastography methods have been applied as tools for evaluating the mechanical properties and ECM content of skeletal muscle. In an effort to develop an ECM altered skeletal muscle model, this study determined the effect of collagen digestion on the passive elastic properties of skeletal muscle. Passive mechanical properties of rat diaphragms were evaluated in various degrees of collagen digestion. Between cyclic loading tests, muscle strips were immersed in various concentrations of clostridium histolyticum derived bacterial collagenase. All samples were later viewed via light microscopy. Cyclic testing revealed linear relationships between passive muscle stiffness and digestion time at multiple concentrations. These results demonstrate that collagenase digestion of the ECM in skeletal muscle could be used as a simple and reliable model of mechanically altered in vitro tissue samples.

  16. [Morphohistochemical study of skeletal muscles in rats after experimental flight on "Kosmos-1887"].

    PubMed

    Il'ina-Kakueva, E I

    1990-01-01

    Morphometric and histochemical methods were used to examine the soleus, gastrocnemius (medial portion), quadriceps femoris (central portion) and biceps brachii muscles of Wistar SPF rats two days after the 13-day flight on Cosmos-1887. It was found that significant atrophy developed only in the soleus muscle. The space flight did not change the percentage content of slow (type I) and fast (type II) fibers in fast twitch muscles. During two days at 1 g the slow soleus muscle developed substantial circulation disorders, which led to interstitial edema and necrotic changes. The gastrocnemius muscle showed small foci containing necrotic myofibers. Two days after recovery no glycogen aggregates were seen in myofibers, which were previously observed in other rats examined 4--8 hours after flight. An initial stage of muscle readaptation to 1 g occurred, when NAD.H2-dehydrogenase activity was decreased.

  17. Isolation and characterization of primary skeletal muscle satellite cells from rats.

    PubMed

    Liu, Yuan; Chen, Sifan; Li, Wenxue; Du, Hongyan; Zhu, Wei

    2012-11-01

    The purpose of this study was to isolate and characterize skeletal muscle satellite cells from rats using tissue block culture method. Specific Pathogen Free (SPF) level Sprague-Dawley (SD) rats were used to isolate skeletal muscle satellite cells. Morphology, expression and distribution of α-actin and Desmin within the cytoplasm of skeletal muscle satellite cells were compared with those of C2C12 myoblasts. The results showed that tissue block culturing method achieved robust proliferation and excellent differentiation of skeletal muscle satellite cells. Immunofluorescence and immunohistochemistry results showed that α-actin and Desmin proteins were expressed in the cytoplasm of both skeletal muscle satellite cells and myoblasts. We concluded that tissue block culturing method can obtain highly purified skeletal muscle satellite cells with robust proliferation and excellent differentiation capabilities.

  18. Mitochondrial respiration in muscle and liver from cold-acclimated hypothyroid rats.

    PubMed

    Zaninovich, Angel A; Rebagliati, Ines; Raices, Marcela; Ricci, Conrado; Hagmuller, Karl

    2003-10-01

    The effects of long-term cold exposure on muscle and liver mitochondrial oxygen consumption in hypothyroid and normal rats were examined. Thyroid ablation was performed after 8-wk acclimation to 4 degrees C. Hypothyroid and normal controls remained in the cold for an additional 8 wk. At the end of 16-wk cold exposure, all hypothyroid rats were alive and normothermic and had normal body weight. At ambient temperature (24 degrees C), thyroid ablation induced a 65% fall in muscle mitochondrial oxygen consumption, which was reversed by thyroxine but not by norepinephrine administration. After cold acclimation was reached, suppression of thyroid function reduced muscle mitochondrial respiration by 30%, but the hypothyroid values remained about threefold higher than those in hypothyroid muscle in the warm. Blockade of beta- and alpha1-adrenergic receptors in both hypothyroid and normal rats produced hypothermia in vivo and a fall in muscle, liver, and brown adipose tissue mitochondria respiration in vitro. In normal rats, cold acclimation enhanced muscle respiration by 35%, in liver 18%, and in brown adipose tissue 450% over values in the warm. The results demonstrate that thyroid hormones, in the presence of norepinephrine, are major determinants of thermogenic activity in muscle and liver of cold-acclimated rats. After thyroid ablation, cold-induced nonshivering thermogenesis replaced 3,5,3'-triiodothyronine-induced thermogenesis, and normal body temperature was maintained.

  19. Metabolic adaptations of skeletal muscle to voluntary wheel running exercise in hypertensive heart failure rats.

    PubMed

    Schultz, R L; Kullman, E L; Waters, R P; Huang, H; Kirwan, J P; Gerdes, A M; Swallow, J G

    2013-01-01

    The Spontaneously Hypertensive Heart Failure (SHHF) rat mimics the human progression of hypertension from hypertrophy to heart failure. However, it is unknown whether SHHF animals can exercise at sufficient levels to observe beneficial biochemical adaptations in skeletal muscle. Thirty-seven female SHHF and Wistar-Furth (WF) rats were randomized to sedentary (SHHFsed and WFsed) and exercise groups (SHHFex and WFex). The exercise groups had access to running wheels from 6-22 months of age. Hindlimb muscles were obtained for metabolic measures that included mitochondrial enzyme function and expression, and glycogen utilization. The SHHFex rats ran a greater distance and duration as compared to the WFex rats (P<0.05), but the WFex rats ran at a faster speed (P<0.05). Skeletal muscle citrate synthase and beta-hydroxyacyl-CoA dehydrogenase enzyme activity was not altered in the SHHFex group, but was increased (P<0.05) in the WFex animals. Citrate synthase protein and gene expression were unchanged in SHHFex animals, but were increased in WFex rats (P<0.05). In the WFex animals muscle glycogen was significantly depleted after exercise (P<0.05), but not in the SHHFex group. We conclude that despite robust amounts of aerobic activity, voluntary wheel running exercise was not sufficiently intense to improve the oxidative capacity of skeletal muscle in adult SHHF animals, indicating an inability to compensate for declining heart function by improving peripheral oxidative adaptations in the skeletal muscle.

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

    PubMed

    Plant, David R; Beitzel, Felice; Lynch, Gordon S

    2005-06-01

    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.

  1. The effect of creatine supplementation on mass and performance of rat skeletal muscle.

    PubMed

    Young, Robert E; Young, John C

    2007-08-09

    This study investigated the effect of dietary creatine supplementation on hypertrophy and performance of rat skeletal muscle. Male Sprague-Dawley rats underwent either tibialis anterior ablation or partial ablation of the plantaris/gastrocnemius to induce compensatory hypertrophy of the extensor digitorum longus (EDL) or soleus respectively, or sham surgery. Creatine (300 mg/kg) was administered to one half of each group for 5 weeks, after which force production was measured. With the leg fixed at the knee and ankle, the distal tendon of the EDL or soleus was attached to a force transducer and the muscle was electrically stimulated via the sciatic nerve. Synergist ablation resulted in a significant increase in EDL mass and in soleus mass relative to control muscles. However, no effect of creatine supplementation on muscle mass or performance was found between control and either group of creatine-treated rats. Despite an apparent increase in muscle creatine content, creatine supplementation did not augment muscle hypertrophy or force production in rat EDL or soleus muscle, providing evidence that the potential benefits of creatine supplementation are not due to a direct effect on muscle but rather to an enhanced ability to train.

  2. The bile duct ligated rat: A relevant model to study muscle mass loss in cirrhosis.

    PubMed

    Bosoi, Cristina R; Oliveira, Mariana M; Ochoa-Sanchez, Rafael; Tremblay, Mélanie; Ten Have, Gabriella A; Deutz, Nicolaas E; Rose, Christopher F; Bemeur, Chantal

    2017-04-01

    Muscle mass loss and hepatic encephalopathy (complex neuropsychiatric disorder) are serious complications of chronic liver disease (cirrhosis) which impact negatively on clinical outcome and quality of life and increase mortality. Liver disease leads to hyperammonemia and ammonia toxicity is believed to play a major role in the pathogenesis of hepatic encephalopathy. However, the effects of ammonia are not brain-specific and therefore may also affect other organs and tissues including muscle. The precise pathophysiological mechanisms underlying muscle wasting in chronic liver disease remains to be elucidated. In the present study, we characterized body composition as well as muscle protein synthesis in cirrhotic rats with hepatic encephalopathy using the 6-week bile duct ligation (BDL) model which recapitulates the main features of cirrhosis. Compared to sham-operated control animals, BDL rats display significant decreased gain in body weight, altered body composition, decreased gastrocnemius muscle mass and circumference as well as altered muscle morphology. Muscle protein synthesis was also significantly reduced in BDL rats compared to control animals. These findings demonstrate that the 6-week BDL experimental rat is a relevant model to study liver disease-induced muscle mass loss.

  3. Electrophysiological, histochemical, and hormonal adaptation of rat muscle after prolonged hindlimb suspension

    NASA Astrophysics Data System (ADS)

    Kourtidou-Papadeli, Chrysoula; Kyparos, Antonios; Albani, Maria; Frossinis, Athanasios; Papadelis, Christos L.; Bamidis, Panagiotis; Vivas, Ana; Guiba-Tziampiri, Olympia

    2004-05-01

    The perspective of long-duration flights for future exploration, imply more research in the field of human adaptation. Previous studies in rat muscles hindlimb suspension (HLS), indicated muscle atrophy and a change of fibre composition from slow-to-fast twitch types. However, the contractile responses to long-term unloading is still unclear. Fifteen adult Wistar rats were studied in 45 and 70 days of muscle unweighting and soleus (SOL) muscle as well as extensor digitorum longus (EDL) were prepared for electrophysiological recordings (single, twitch, tetanic contraction and fatigue) and histochemical stainings. The loss of muscle mass observed was greater in the soleus muscle. The analysis of electrophysiological properties of both EDL and SOL showed significant main effects of group, of number of unweighting days and fatigue properties. Single contraction for soleus muscle remained unchanged but there was statistically significant difference for tetanic contraction and fatigue. Fatigue index showed a decrease for the control rats, but increase for the HLS rats. According to the histochemical findings there was a shift from oxidative to glycolytic metabolism during HLS. The data suggested that muscles atrophied, but they presented an adaptation pattern, while their endurance in fatigue was decreased.

  4. Coexistence of twitch potentiation and tetanic force decline in rat hindlimb muscle

    NASA Technical Reports Server (NTRS)

    Rankin, Lucinda L.; Enoka, Roger M.; Volz, Kathryn A.; Stuart, Douglas G.

    1988-01-01

    The effect of whole-muscle fatigue on the isometric twitch was investigated in various hindlimb muscles of anesthetized rats, using an experimental protocol designed to assess the levels of fatigability in motor units. The results of EMG and force measurements revealed the existence of a linear relationship between fatigability and the magnitude of the twitch force following the fatigue test in both soleus and extensor digitorum longus muscles.

  5. Leucine Protects Against Skeletal Muscle Atrophy in Lipopolysaccharide-Challenged Rats.

    PubMed

    Wan, Jin; Chen, Daiwen; Yu, Bing; Luo, Yuheng; Mao, Xiangbing; Zheng, Ping; Yu, Jie; Luo, Junqiu; He, Jun

    2017-01-01

    Skeletal muscle atrophy is a decrease in muscle mass that occurs when protein degradation exceeds protein synthesis. Leucine (Leu), an essential branched-chain amino acid in animal nutrition, regulates skeletal muscle protein metabolism. Two experiments were conducted to evaluate whether Leu could alleviate lipopolysaccharide (LPS)-induced skeletal muscle wasting by modulating skeletal muscle protein synthesis and degradation. A total of 24 rats were randomly allocated into three groups (n = 8): (1) non-challenged control; (2) LPS-challenged control; and (3) LPS +3.0% Leu. Rats were fed with control or Leu-supplemented (part of the casein was replaced with 3.0% Leu) diets throughout the trial and were injected intraperitoneally with sterile saline or LPS at days 6, 11, 16, and 21. On the morning of day 22, serum samples were collected and rats were then sacrificed for liver and muscle analysis. In vitro protein degradation, nuclear factor-κB (NF-κB) activity, and proteolytic enzyme activities of the muscles from immune-challenged rats were also measured. Our results showed that the LPS challenge resulted in not only enhanced serum interleukin-1 and liver C-reactive protein (CRP) concentrations but also decreased the average daily body weight gain and muscle fiber diameter. However, dietary Leu inclusion attenuated the increase in CRP level and the decrease in muscle fiber diameter. Importantly, the LPS challenge caused a significant elevation in the muscle proteolysis rate, but dietary Leu supplementation significantly blocked the muscle proteolysis. The mRNA expression of NF-κB, muscle atrophy F-box (MAFbx), and muscle ring finger 1 (MuRF1) was upregulated by the LPS challenge in gastrocnemius muscles, but was downregulated by Leu supplementation. Interestingly, when muscles from the LPS-challenged rats were incubated with Leu in vitro, proteasome-, calpain-, and cathepsin-L-dependent muscle proteolysis and NF-κB activity were decreased. Collectively, the

  6. Changes in rat soleus muscle phenotype consecutive to a growth in hypergravity followed by normogravity.

    PubMed

    Picquet, F; Bouet, V; Cochon, L; Lacour, M; Falempin, M

    2005-07-01

    It has been demonstrated that a long-term stay in hypergravity (HG: 2G) modified the phenotype and the contractile properties of rat soleus muscle. The ability of this muscle to contract was drastically reduced, which is a sign of anticipated aging. Consequently, our aim was to determine whether rats conceived, born, and reared in hypergravity showed adaptative capacities in normogravity (NG: 1G). This study was performed on rats divided into two series: the first was reared in HG until 100 days and was submitted to normogravity until 115 to 220 postnatal days (HG-NG rats); the second was made up of age paired groups reared in normogravity (NG rats). The contractile, morphological, and phenotypical properties of soleus muscle were studied. Our results showed that the NG rats were characterized by coexpressions of slow and fast myosin, respectively, 76.5 and 23.5% at 115 days. During their postnatal maturation, the fast isoform was gradually replaced by slow myosin. At 220 days, the relative proportions were respectively 91.05% and 8.95%. From 115 to 220 days, the HG-NG rats expressed 100% of slow myosin isoform and they presented a slower contractile behavior compared with their age-matched groups; at 115 days, the whole muscle contraction time was increased by 35%, and by 15%, at 220 days. Our study underlined the importance of gravity in the muscular development and suggested the existence of critical periods in muscle phenotype installation.

  7. Effects of oxygen deprivation on incubated rat soleus muscle

    NASA Technical Reports Server (NTRS)

    Fagan, Julie M.; Tischler, Marc E.

    1989-01-01

    Isolated soleus muscle deprived of oxygen produces more lactate and alanine than oxygen-supplied muscle. Oxygenated muscle synthesized glutamine, while anoxic muscle used this amino acid. Oxygen deprivation decreased adenine nucleotides leading to the efflux of nucleosides. Protein synthesis and degradation responded differently to anoxia. Synthesis almost completely ceased, while proteolysis increased. Therefore, protein degradation in soleus muscle is enhanced when energy supplies and oxygen tension are low.

  8. Differential RNA Expression Profile of Skeletal Muscle Induced by Experimental Autoimmune Myasthenia Gravis in Rats

    PubMed Central

    Kaminski, Henry J.; Himuro, Keiichi; Alshaikh, Jumana; Gong, Bendi; Cheng, Georgiana; Kusner, Linda L.

    2016-01-01

    The differential susceptibility of skeletal muscle by myasthenia gravis (MG) is not well understood. We utilized RNA expression profiling of extraocular muscle (EOM), diaphragm (DIA), and extensor digitorum (EDL) of rats with experimental autoimmune MG (EAMG) to evaluate the hypothesis that muscles respond differentially to injury produced by EAMG. EAMG was induced in female Lewis rats by immunization with acetylcholine receptor purified from the electric organ of the Torpedo. Six weeks later after rats had developed weakness and serum antibodies directed against the AChR, animals underwent euthanasia and RNA profiling performed on DIA, EDL, and EOM. Profiling results were validated by qPCR. Across the three muscles between the experiment and control groups, 359 probes (1.16%) with greater than 2-fold changes in expression in 7 of 9 series pairwise comparisons from 31,090 probes were identified with approximately two-thirds being increased. The three muscles shared 16 genes with increased expression and 6 reduced expression. Functional annotation demonstrated that these common expression changes fell predominantly into categories of metabolism, stress response, and signaling. Evaluation of specific gene function indicated that EAMG led to a change to oxidative metabolism. Genes related to muscle regeneration and suppression of immune response were activated. Evidence of a differential immune response among muscles was not evident. Each muscle had a distinct RNA profile but with commonality in gene categories expressed that are focused on muscle repair, moderation of inflammation, and oxidative metabolism. PMID:27891095

  9. Effect of endurance training on glucose transport capacity and glucose transporter expression in rat skeletal muscle

    SciTech Connect

    Ploug, T.; Stallknecht, B.M.; Pedersen, O.; Kahn, B.B.; Ohkuwa, T.; Vinten, J.; Galbo, H. )

    1990-12-01

    The effect of 10 wk endurance swim training on 3-O-methylglucose (3-MG) uptake (at 40 mM 3-MG) in skeletal muscle was studied in the perfused rat hindquarter. Training resulted in an increase of approximately 33% for maximum insulin-stimulated 3-MG transport in fast-twitch red fibers and an increase of approximately 33% for contraction-stimulated transport in slow-twitch red fibers compared with nonexercised sedentary muscle. A fully additive effect of insulin and contractions was observed both in trained and untrained muscle. Compared with transport in control rats subjected to an almost exhaustive single exercise session the day before experiment both maximum insulin- and contraction-stimulated transport rates were increased in all muscle types in trained rats. Accordingly, the increased glucose transport capacity in trained muscle was not due to a residual effect of the last training session. Half-times for reversal of contraction-induced glucose transport were similar in trained and untrained muscles. The concentrations of mRNA for GLUT-1 (the erythrocyte-brain-Hep G2 glucose transporter) and GLUT-4 (the adipocyte-muscle glucose transporter) were increased approximately twofold by training in fast-twitch red muscle fibers. In parallel to this, Western blot demonstrated a approximately 47% increase in GLUT-1 protein and a approximately 31% increase in GLUT-4 protein. This indicates that the increases in maximum velocity for 3-MG transport in trained muscle is due to an increased number of glucose transporters.

  10. Changes in activity and structure of jaw muscles in Parkinson's disease model rats.

    PubMed

    Nakamura, S; Kawai, N; Ohnuki, Y; Saeki, Y; Korfage, J A M; Langenbach, G E J; Kitayama, T; Watanabe, M; Sano, R; Tanne, K; Tanaka, E

    2013-03-01

    Parkinson's disease (PD), a major neurological disease, is characterised by a marked loss of dopaminergic neurons in the substantia nigra. Patients with PD frequently show chewing and swallowing dysfunctions, but little is known about the characteristics of their stomatognathic functions. The purpose of this study was to evaluate the influence of PD on jaw muscle fibre and functions. PD model rats were made by means of the injection of 6-hydroxydopamine (6-OHDA) into the striatum of 8-week-old Sprague-Dawley male rats. Five weeks after the injection, a radio-telemetric device was implanted to record muscle activity continuously from the superficial masseter and anterior belly of digastric muscles. Muscle activity was recorded for 3 days and was evaluated by the total duration of muscle activity per day (duty time). After recording the muscle activities, jaw muscles were isolated for immunohistochemical and PCR analyses. In PD model rats, the following findings of the digastrics muscles verify that compared to the control group: (i) the higher duty time exceeding 5% of the peak activity level, (ii) the higher expression of the mRNA of myosin heavy chain type I, and (iii) the tendency for fast to slow fibre-type transition. With respect to the masseter muscle, there were no significant differences in all analyses. In conclusion, PD leads to the changes in the jaw behaviours, resulting in a PD-specific chewing and swallowing dysfunctions.

  11. Assessment of the Potential Role of Muscle Spindle Mechanoreceptor Afferents in Chronic Muscle Pain in the Rat Masseter Muscle

    PubMed Central

    Sadeghi, Somayeh; Athanassiadis, Tuija; Caram Salas, Nadia; Auclair, François; Thivierge, Benoît; Arsenault, Isabel; Rompré, Pierre; Westberg, Karl-Gunnar; Kolta, Arlette

    2010-01-01

    Background The phenotype of large diameter sensory afferent neurons changes in several models of neuropathic pain. We asked if similar changes also occur in “functional” pain syndromes. Methodology/Principal Findings Acidic saline (AS, pH 4.0) injections into the masseter muscle were used to induce persistent myalgia. Controls received saline at pH 7.2. Nocifensive responses of Experimental rats to applications of Von Frey Filaments to the masseters were above control levels 1–38 days post-injection. This effect was bilateral. Expression of c-Fos in the Trigeminal Mesencephalic Nucleus (NVmes), which contains the somata of masseter muscle spindle afferents (MSA), was above baseline levels 1 and 4 days after AS. The resting membrane potentials of neurons exposed to AS (n = 167) were hyperpolarized when compared to their control counterparts (n = 141), as were their thresholds for firing, high frequency membrane oscillations (HFMO), bursting, inward and outward rectification. The amplitude of HFMO was increased and spontaneous ectopic firing occurred in 10% of acid-exposed neurons, but never in Controls. These changes appeared within the same time frame as the observed nocifensive behaviour. Ectopic action potentials can travel centrally, but also antidromically to the peripheral terminals of MSA where they could cause neurotransmitter release and activation of adjacent fibre terminals. Using immunohistochemistry, we confirmed that annulospiral endings of masseter MSA express the glutamate vesicular transporter VGLUT1, indicating that they can release glutamate. Many capsules also contained fine fibers that were labelled by markers associated with nociceptors (calcitonin gene-related peptide, Substance P, P2X3 receptors and TRPV1 receptors) and that expressed the metabotropic glutamate receptor, mGluR5. Antagonists of glutamatergic receptors given together with the 2nd injection of AS prevented the hypersensitivity observed bilaterally but were

  12. Intercostal muscle motor behavior during tracheal occlusion conditioning in conscious rats

    PubMed Central

    Jaiswal, Poonam B.

    2016-01-01

    A respiratory load compensation response is characterized by increases in activation of primary respiratory muscles and/or recruitment of accessory respiratory muscles. The contribution of the external intercostal (EI) muscles, which are a primary respiratory muscle group, during normal and loaded breathing remains poorly understood in conscious animals. Consciousness has a significant role on modulation of respiratory activity, as it is required for the integration of behavioral respiratory responses and voluntary control of breathing. Studies of respiratory load compensation have been predominantly focused in anesthetized animals, which make their comparison to conscious load compensation responses challenging. Using our established model of intrinsic transient tracheal occlusions (ITTO), our aim was to evaluate the motor behavior of EI muscles during normal and loaded breathing in conscious rats. We hypothesized that 1) conscious rats exposed to ITTO will recruit the EI muscles with an increased electromyogram (EMG) activation and 2) repeated ITTO for 10 days would potentiate the baseline EMG activity of this muscle in conscious rats. Our results demonstrate that conscious rats exposed to ITTO respond by recruiting the EI muscle with a significantly increased EMG activation. This response to occlusion remained consistent over the 10-day experimental period with little or no effect of repeated ITTO exposure on the baseline ∫EI EMG amplitude activity. The pattern of activation of the EI muscle in response to an ITTO is discussed in detail. The results from the present study demonstrate the importance of EI muscles during unloaded breathing and respiratory load compensation in conscious rats. PMID:26823339

  13. Titin isoform size is not correlated with thin filament length in rat skeletal muscle

    PubMed Central

    Greaser, Marion L.; Pleitner, Jonathan M.

    2014-01-01

    The mechanisms controlling thin filament length (TFL) in muscle remain controversial. It was recently reported that TFL was related to titin size, and that the latter might be involved in TFL determination. Titin plays several crucial roles in the sarcomere, but its function as it pertains to the thin filament has not been explored. We tested this relationship using several muscles from wild type rats and from a mutant rat model (Greaser et al., 2008) which results in increased titin size. Myofibrils were isolated from skeletal muscles [extensor digitorum longus (EDL), external oblique (EO), gastrocnemius (GAS), longissimus dorsi (LD), psoas major (PM), and tibialis anterior(TA)] using both adult wild type (WT) and homozygous mutant (HM) rats (n = 6 each). Phalloidin and antibodies against tropomodulin-4 (Tmod-4) and nebulin's N-terminus were used to determine TFL. The WT rats studied express skeletal muscle titin sizes ranging from 3.2 to 3.7 MDa, while the HM rats express a giant titin isoform sized at 3.8 MDa. No differences in phalloidin based TFL, nebulin distance, or Tmod distance were observed across genotypes. However, the HM rats demonstrated a significantly increased (p < 0.01) rest sarcomere length relative to the WT phenotype. It appears that the increased titin size, predominantly observed in HM rats' middle Ig domain, allows for increased extensibility. The data indicates that, although titin performs many sarcomeric functions, its correlation with TFL and structure could not be demonstrated in the rat. PMID:24550844

  14. Enhancement of Skeletal Muscle in Aged Rats Following High-Intensity Stretch-Shortening Contraction Training.

    PubMed

    Rader, Erik P; Naimo, Marshall A; Layner, Kayla N; Triscuit, Alyssa M; Chetlin, Robert D; Ensey, James; Baker, Brent A

    2016-08-03

    Exercise is the most accessible, efficacious, and multifactorial intervention to improve health and treat chronic disease. High-intensity resistance exercise, in particular, also maximizes skeletal muscle size and strength-outcomes crucial at advanced age. However, such training is capable of inducing muscle maladaptation when misapplied at old age. Therefore, characterization of parameters (e.g., mode and frequency) that foster adaptation is an active research area. To address this issue, we utilized a rodent model that allowed training at maximal intensity in terms of muscle activation and tested the hypothesis that muscles of old rats adapt to stretch-shortening contraction (SSC) training, provided the training frequency is sufficiently low. At termination of training, normalized muscle mass (i.e., muscle mass divided by tibia length) and muscle quality (isometric force divided by normalized muscle mass) were determined. For young rats, normalized muscle mass increased by ∼20% regardless of training frequency. No difference was observed for muscle quality values after 2 days versus 3 days per week training (0.65 ± 0.09 N/mg/mm vs. 0.59 ± 0.05 N/mg/mm, respectively). For old rats following 3 days per week training, normalized muscle mass was unaltered and muscle quality was 30% lower than young levels. Following 2 days per week training at old age, normalized muscle mass increased by 17% and muscle quality was restored to young levels. To investigate this enhanced response, oxidative stress was assessed by lipid peroxidation quantification. For young rats, lipid peroxidation levels were unaltered by training. With aging, baseline levels of lipid peroxidation increased by 1.5-fold. For old rats, only 2 days per week training decreased lipid peroxidation to levels indistinguishable from young values. These results imply that, appropriately scheduled high-intensity SSC training at old age is capable of restoring muscle to a younger phenotype in terms

  15. Purinergic Effects on Na,K-ATPase Activity Differ in Rat and Human Skeletal Muscle

    PubMed Central

    Juel, Carsten; Nordsborg, Nikolai B.; Bangsbo, Jens

    2014-01-01

    Background P2Y receptor activation may link the effect of purines to increased maximal in vitro activity of the Na,K-ATPase in rat muscle. The hypothesis that a similar mechanism is present in human skeletal muscle was investigated with membranes from rat and human skeletal muscle. Results Membranes purified from rat and human muscles were used in the Na,K-ATPase assay. Incubation with ADP, the stable ADP analogue MeS-ADP and UDP increased the Na+ dependent Na,K-ATPase activity in rat muscle membranes, whereas similar treatments of human muscle membranes lowered the Na,K-ATPase activity. UTP incubation resulted in unchanged Na,K-ATPase activity in humans, but pre-incubation with the antagonist suramin resulted in inhibition with UTP, suggesting that P2Y receptors are involved. The Na,K-ATPase in membranes from both rat and human could be stimulated by protein kinase A and C activation. Thus, protein kinase A and C activation can increase Na,K-ATPase activity in human muscle but not via P2Y receptor stimulation. Conclusion The inhibitory effects of most purines (with the exception of UTP) in human muscle membranes are probably due to mass law inhibition of ATP hydrolysis. This inhibition could be blurred in rat due to receptor mediated activation of the Na,K-ATPase. The different effects could be related to a high density of ADP sensitive P2Y1 and P2Y13 receptors in rat, whereas the UTP sensitive P2Y11 could be more abundant in human. Alternatively, rat could possesses a mechanism for protein-protein interaction between P2Y receptors and the Na,K-ATPase, and this mechanism could be absent in human skeletal muscle (perhaps with the exception of the UTP sensitive P2Y11 receptor). Perspective Rat muscle is not a reliable model for purinergic effects on Na,K-ATPase in human skeletal muscle. PMID:24614174

  16. Experimental evaluation of the effects of pravastatin on electrophysiological parameters of rat skeletal muscle.

    PubMed

    Pierno, S; De Luca, A; Tricarico, D; Ferrannini, E; Conte, T; D'Alò, G; Camerino, D C

    1992-11-01

    The effects of daily chronic treatment for 6 months with pravastatin was evaluated on the performance of the skeletal muscle system of different rat groups. At all doses (0.1 mg/kg-20 mg/kg) the righting reflex and the electromyographic signals observed in vivo did not show any abnormality. At the end of the treatment the Extensor digitorum longus muscles were dissected from treated and control rats and their passive and active electrical parameters were analyzed in vitro by standard microelectrodes technique. Pravastatin did not modify the chloride conductance nor the excitability characteristics of the fibers. Chronic treatment with pravastatin does not produce any alteration of skeletal muscle function.

  17. Effect of denervation or unweighting on GLUT-4 protein in rat soleus muscle

    NASA Technical Reports Server (NTRS)

    Henriksen, Erik J.; Rodnick, Kenneth J.; Mondon, Carl E.; James, David E.; Holloszy, John O.

    1991-01-01

    The study is intended to test the hypothesis that the decreased capacity for glucose transport in the denervated rat soleus and the increased capacity for glucose transport in the unweighted rat soleus are related to changes in the expression of the regulatable glucose transporter protein in skeletal muscle (GLUT-4). Results obtained indicate that altered GLUT-4 expression may be a major contributor to the changes in insulin-stimulated glucose transport that are observed with denervation and unweighting. It is concluded that muscle activity is an important factor in the regulation of the GLUT-4 expression in skeletal muscle.

  18. [Skeletal muscle mixed fiber tissue metabolism in rats after a flight on the Kosmos-690 biosatellite].

    PubMed

    Gaevskaia, M S; Belitskaia, R A; Kolganova, N S; Kolchina, E V; Kurkina, L M

    1979-01-01

    On the R+O day the quadriceps muscle of rats showed a decrease in the content of T protein and an inhibition of LDH activity of sacroplasmatic proteins. These changes resulted from the combined affect of space flight factors and gamma-irradiation, and may be considered as a decline of compensatory synthetic processes responsible for the recovery of muscle proteins in weightlessness. Inhibition of the age-associated shift of the M:H ratio of LDH found on the R+25 day can be attributed to the inhibitory effect of gamma-irradiation. No change in the content of glycogen in the gastrocnemius muscle of flight rats was noted.

  19. Extracellular calcium sensing in rat aortic vascular smooth muscle cells

    SciTech Connect

    Smajilovic, Sanela; Hansen, Jakob Lerche; Christoffersen, Tue E.H.

    2006-10-06

    Extracellular calcium (Ca2+o) can act as a first messenger in many cell types through a G protein-coupled receptor, calcium-sensing receptor (CaR). It is still debated whether the CaR is expressed in vascular smooth muscle cells (VSMCs). Here, we report the expression of CaR mRNA and protein in rat aortic VSMCs and show that Ca2+o stimulates proliferation of the cells. The effects of Ca2+o were attenuated by pre-treatment with MAPK kinase 1 (MEK1) inhibitor, as well as an allosteric modulator, NPS 2390. Furthermore, stimulation of the VSMCs with Ca2+o-induced phosphorylation of ERK1/2, but surprisingly did not cause inositol phosphate accumulation. We were not able to conclusively state that the CaR mediates Ca2+o-induced cell proliferation. Rather, an additional calcium-sensing mechanism may exist. Our findings may be of importance with regard to atherosclerosis, an inflammatory disease characterized by abnormal proliferation of VSMCs and high local levels of calcium.

  20. The production of denervation-like changes in rat muscle by colchicine, without interference with axonal transport or muscle activity.

    PubMed Central

    Cangiano, A; Fried, J A

    1977-01-01

    1. Rat extensor digitorum longus (EDL) muscles were examined after colchicine treatment of the sciatic nerve. Colchicine was applied in one of two ways: (i) a single sub-epineural injection; (ii) a chronically implanted silicone cuff. 2. After the sub-epineural injection, the entire membrane of muscle fibres became sensitive to iontophoretically applied acetylcholine and the muscle action potentials became resistant to tetrodotoxin. However, the majority of these fibres were found to be normally innervated. 3. These effects were not restricted to the EDL muscle of the colchicine injected side but were also found in the EDL muscle of the contralateral side, indicating that the action of colchicine was systemic. 4. In the treated sciatic nerve there was a partial block of axonal transport of 3H-labelled proteins, which correlated with a partial paralysis of the ipsilateral leg. However, axoplasmic transport was found to be normal in the contralateral sciatic nerve and the contralateral limb was not paralysed despite the supersensitivity of the investigated muscle on that side. 5. When colchicine was applied with a silicone cuff, denervation-like changes were confined to the ipsilateral EDL muscle. However, impulse conduction block at the level of the cuff was usually observed. 6. It is concluded that (i) colchicine can produce denervation-like changes in normally active muscle without blocking axoplasmic transport, through an action probably exerted directly on the muscle membrane, and (ii) that colchicine-cuff experiments failed to provide unambiguous evidence in support of the existence of neurotrophic influences on the muscle membrane. PMID:66309

  1. Statin-induced myopathy in the rat: relationship between systemic exposure, muscle exposure and myopathy.

    PubMed

    Sidaway, J; Wang, Y; Marsden, A M; Orton, T C; Westwood, F R; Azuma, C T; Scott, R C

    2009-01-01

    Rare instances of myopathy are associated with all statins, but cerivastatin was withdrawn from clinical use due to a greater incidence of myopathy. The mechanism of statin-induced myopathy with respect to tissue disposition was investigated by measuring the systemic, hepatic, and skeletal muscle exposure of cerivastatin, rosuvastatin, and simvastatin in rats before and after muscle damage. The development of myopathy was not associated with the accumulation of statins in skeletal muscle. For each statin exposure was equivalent in muscles irrespective of their fibre-type sensitivity to myopathy. The low amount of each statin in skeletal muscle relative to the liver does not support a significant role for transporters in the disposition of statins in skeletal muscle. Finally, the concentration of cerivastatin necessary to cause necrosis in skeletal muscle was considerably lower than rosuvastatin or simvastatin, supporting the concept cerivastatin is intrinsically more myotoxic than other statins.

  2. Prevention of metabolic alterations caused by suspension hypokinesia in leg muscles of rats

    NASA Technical Reports Server (NTRS)

    Tischler, M. E.; Jaspers, S. R.; Fagan, J. M.

    1983-01-01

    Rats were subjected to tail-cast suspension hypokinesia for 6 days with one leg immobilized in dorsal flexion by casting. Control animals were also tail-casted. The soleus, gastrocnemius and plantaris muscles of uncasted hypokinetic legs were smaller than control muscles. Dorsal flexion prevented atrophy of these muscles and caused the soleus to hypertrophy. The anterior muscles were unaffected by hypokinesia. The smaller size of the soleus of the uncasted leg relative to the dorsal flexed and weight bearing limbs correlated with slower protein synthesis and faster proteolysis. The capacity of this muscle to synthesize glutamine (gln), which carries nitrogenous waste from muscle was also measured. Although tissue homogenates showed higher activities of gln synthetase, the rate of de novo synthesis was not altered in intact muscle but the tissue ratio of gln/glutamate was decreased. Glutamate and ATP were not limiting for gln synthesis, but availability of ammonia may be a limiting factor for this process in hypokinesia.

  3. beta-adrenergic effects on carbohydrate metabolism in the unweighted rat soleus muscle

    NASA Technical Reports Server (NTRS)

    Kirby, Christopher R.; Tischler, Marc E.

    1990-01-01

    The effect of unweighting on the response of the soleus-muscle carbohydrate metabolism to a beta-adrenergic agonist (isoproterenol) was investigated in rats that were subjected to three days of tail-cast suspension. It was found that isoproterenol promoted glycogen degradation in soleus from suspended rats to a higher degree than in weighted soleus from control rats, and had no effect in unweighted digitorum longus. However, isoproterenol did not have a greater inhibitory effect on the net uptake of tritium-labeled 2-deoxy-glucose by the unweighted soleus and that isoproterenol inhibited hexose phosphorylation less in the unweighted than in the control muscle.

  4. Transcriptional profiling of rat skeletal muscle hypertrophy under restriction of blood flow.

    PubMed

    Xu, Shouyu; Liu, Xueyun; Chen, Zhenhuang; Li, Gaoquan; Chen, Qin; Zhou, Guoqing; Ma, Ruijie; Yao, Xinmiao; Huang, Xiao

    2016-12-15

    Blood flow restriction (BFR) under low-intensity resistance training (LIRT) can produce similar effects upon muscles to that of high-intensity resistance training (HIRT) while overcoming many of the restrictions to HIRT that occurs in a clinical setting. However, the potential molecular mechanisms of BFR induced muscle hypertrophy remain largely unknown. Here, using a BFR rat model, we aim to better elucidate the mechanisms regulating muscle hypertrophy as induced by BFR and reveal possible clinical therapeutic targets for atrophy cases. We performed genome wide screening with microarray analysis to identify unique differentially expressed genes during rat muscle hypertrophy. We then successfully separated the differentially expressed genes from BRF treated soleus samples by comparing the Affymetrix rat Genome U34 2.0 array with the control. Using qRT-PCR and immunohistochemistry (IHC) we also analyzed other related differentially expressed genes. Results suggested that muscle hypertrophy induced by BFR is essentially regulated by the rate of protein turnover. Specifically, PI3K/AKT and MAPK pathways act as positive regulators in controlling protein synthesis where ubiquitin-proteasome acts as a negative regulator. This represents the first general genome wide level investigation of the gene expression profile in the rat soleus after BFR treatment. This may aid our understanding of the molecular mechanisms regulating and controlling muscle hypertrophy and provide support to the BFR strategies aiming to prevent muscle atrophy in a clinical setting.

  5. Lithium Visibility in Rat Brain and Muscle in Vivoby 7Li NMR Imaging

    NASA Astrophysics Data System (ADS)

    Komoroski, Richard A.; Pearce, John M.; Newton, Joseph E. O.

    1998-07-01

    The apparent concentration of lithium (Li)in vivowas determined for several regions in the brain and muscle of rats by7Li NMR imaging at 4.7 T with inclusion of an external standard of known concentration and visibility. The average apparent concentrations were 10.1 mM for muscle, and 4.2-5.3 mM for various brain regions under the dosing conditions used. The results were compared to concentrations determinedin vitroby high-resolution7Li NMR spectroscopy of extracts of brain and muscle tissue from the same rats. The comparison provided estimates of the7Li NMR visibility of the Li cation in each tissue region. Although there was considerable scatter of the calculated visibilities among the five rats studied, the results suggested essentially full visibility (96%) for Li in muscle, and somewhat reduced visibility (74-93%) in the various brain regions.

  6. [Contractile properties of skeletal muscles of rats after flight on "Kosmos-1887"].

    PubMed

    Oganov, V S; Skuratova, S A; Murashko, L M

    1991-01-01

    Contractile properties of skeletal muscles of rats were investigated using glycerinated muscle preparations that were obtained from Cosmos-1887 animals flown for 13 days (plus 2 days on the ground) and from rats that remained hypokinetic for 13 days on the ground. In the flow rats, the absolute mass of postural muscles remained unchanged while their relative mass increased; this may be attributed to their enhanced hydration which developed during the first 2 days after landing. Strength losses of the postural muscles were less significant than after previous flights. Comparison of the Cosmos-1887 and hypokinesia control data has shown that even 2-day exposure to 1 G after 13-day flight can modify drastically flight-induced changes.

  7. Electrical Stimulation of Denervated Rat Skeletal Muscle Ameliorates Bone Fragility and Muscle Loss in Early-Stage Disuse Musculoskeletal Atrophy.

    PubMed

    Tamaki, Hiroyuki; Yotani, Kengo; Ogita, Futoshi; Hayao, Keishi; Nakagawa, Kouki; Sugawara, Kazuhiro; Kirimoto, Hikari; Onishi, Hideaki; Kasuga, Norikatsu; Yamamoto, Noriaki

    2017-04-01

    We tested whether daily muscle electrical stimulation (ES) can ameliorate the decrease in cortical bone strength as well as muscle and bone geometric and material properties in the early stages of disuse musculoskeletal atrophy. 7-week-old male F344 rats were randomly divided into three groups: age-matched control group (Cont); a sciatic denervation group (DN); and a DN + direct electrical stimulation group (DN + ES). Denervated tibialis anterior (TA) muscle in the DN + ES group received ES with 16 mA at 10 Hz for 30 min/day, 6 days/week. Micro CT, the three-point bending test, and immunohistochemistry were used to characterize cortical bone mechanical, structural, and material properties of tibiae. TA muscle in the DN + ES group showed significant improvement in muscle mass and myofiber cross-sectional area relative to the DN group. Maximal load and stiffness of tibiae, bone mineral density estimated by micro CT, and immunoreactivity of DMP1 in the cortical bone tissue were also significantly greater in the DN + ES group than in the DN group. These results suggest that daily ES-induced muscle contraction treatment reduced the decrease in muscle mass and cortical bone strength in early-stage disuse musculoskeletal atrophy and is associated with a beneficial effect on material properties such as mineralization of cortical bone tissue.

  8. Induction of Muscle Hypertrophy in Rats through Low Intensity Eccentric Contraction.

    PubMed

    Tsumiyama, Wakako; Oki, Sadaaki; Takamiya, Naomi; Umei, Namiko; Shimizu, Michele Eisemann; Ono, Takeya; Otsuka, Akira

    2014-10-01

    [Purpose] The purpose of this study was to examine whether a low intensity exercise using an eccentric contraction would result in skeletal muscle hypertrophy in rats. [Subjects and Methods] Eighteen female Wistar rats were used in this study. The rats were randomly divided into three groups. The control group performed no exercise. The level group ran on a treadmill on a 0° incline. The downhill group ran on a treadmill on a -16° incline. The two exercise groups ran on a treadmill at 16 m/min for 90 minutes, once every three days for a total of twenty sessions. [Results] The muscle wet weights, the relative weight ratios, and the muscle fiber cross-section minor axes of the downhill group were significantly larger than those of the control and level groups. There were no differences in the muscle wet weights, the relative weight ratios, and the muscle fiber cross-section minor axes between the control group and the level group. [Conclusion] The stimulation from the low intensity eccentric contraction may have produced enough mechanical stress to induce muscle hypertrophy without the over-stressing that might have produced muscle fiber damage. These results indicate that this technique may be an effective method of inducing hypertrophy in skeletal muscle.

  9. Effects of aging on the lateral transmission of force in rat skeletal muscle.

    PubMed

    Zhang, Chi; Gao, Yingxin

    2014-03-21

    The age-related reduction in muscle force cannot be fully explained by the loss of muscle fiber mass or degeneration of myofibers. Our previous study showed that changes in lateral transmission of force could affect the total force transmitted to the tendon. The extracellular matrix (ECM) of skeletal muscle plays an important role in lateral transmission of force. The objective of this study was to define the effects of aging on lateral transmission of force in skeletal muscles, and explore possible underlying mechanisms. In vitro contractile tests were performed on extensor digitorum longus (EDL) muscle of young and old rats with series of tenotomy and myotomy. We concluded that lateral transmission of force was impaired in the old rats, and this deficit could be partly due to increased thickness of the ECM induced by aging.

  10. Increased myogenic repressor Id mRNA and protein levels in hindlimb muscles of aged rats.

    PubMed

    Alway, Stephen E; Degens, Hans; Lowe, Dawn A; Krishnamurthy, Gururaj

    2002-02-01

    The objective of this study was to determine if levels of repressors to myogenic regulatory factors (MRFs) differ between muscles from young adult and aged animals. Total RNA from plantaris, gastrocnemius, and soleus muscles of Fischer 344 x Brown Norway rats aged 9 mo (young adult, n = 10) and 37 mo (aged, n = 10) was reverse transcribed and then amplified by PCR. To obtain a semiquantitative measure of the mRNA levels, PCR signals were normalized to cyclophilin or 18S signals from the corresponding reverse transcription product. Normalization to cyclophilin and 18S gave similar results. The mRNA levels of MyoD and myogenin were approximately 275-650% (P < 0.001) and approximately 500-1,100% (P < 0.001) greater, respectively, in muscles from aged compared with young adults. In contrast, the protein levels were lower in plantaris and gastrocnemius muscles and similar in the soleus muscle of aged vs. young adult rats. Id repressor mRNA levels were approximately 300-900% greater in fast and slow muscles of aged animals (P < or = 0.02), and Mist 1 mRNA was approximately 50% greater in the plantaris and gastrocnemius muscles (P < 0.01). The mRNA level of Twist mRNA was not significantly affected by aging. Id-1, Id-2, and Id-3 protein levels were approximately 17-740% greater (P < 0.05) in hindlimb muscles of aged rats compared with young adult rats. The elevated levels of Id mRNA and protein suggest that MRF repressors may play a role in gene regulation of fast and slow muscles in aged rats.

  11. Influence of exercise training on the oxidative capacity of rat abdominal muscles

    NASA Technical Reports Server (NTRS)

    Uribe, J. M.; Stump, C. S.; Tipton, C. M.; Fregosi, R. F.

    1992-01-01

    Our purpose was to determine if endurance exercise training would increase the oxidative capacity of the abdominal expiratory muscles of the rat. Accordingly, 9 male rats were subjected to an endurance training protocol (1 h/day, 6 days/week, 9 weeks) and 9 litter-mates served as controls. Citrate synthase (CS) activity was used as an index of oxidative capacity, and was determined in the following muscles: soleus, plantaris, costal diaphragm, crural diaphragm, and in all four abdominal muscles: rectus abdominis, transversus abdominis, external oblique, and internal oblique. Compared to their non-trained litter-mates, the trained rats had higher peak whole body oxygen consumption rates (+ 16%) and CS activities in plantaris (+34%) and soleus (+36%) muscles. Thus, the training program caused substantial systemic and locomotor muscle adaptations. The CS activity of costal diaphragm was 20% greater in the trained animals, but no difference was observed in crural diaphragm. The CS activity in the abdominal muscles was less than one-half of that in locomotor and diaphragm muscles, and there were no significant changes with training except in the rectus abdominis where a 26% increase was observed. The increase in rectus abdominis CS activity may reflect its role in postural support and/or locomotion, as none of the primary expiratory pumping muscles adapted to the training protocol. The relatively low levels of CS activity in the abdominal muscles suggests that they are not recruited frequently at rest, and the lack of an increase with training indicates that these muscles do not contribute significantly to the increased ventilatory activity accompanying exercise in the rat.

  12. Glycogen stability and glycogen phosphorylase activities in isolated skeletal muscles from rat and toad.

    PubMed

    Goodman, C A; Stephenson, G M

    2000-01-01

    There is increasing evidence that endogenous glycogen depletion may affect excitation-contraction (E-C) coupling events in vertebrate skeletal muscle. One approach employed in physiological investigations of E-C coupling involves the use of mechanically skinned, single fibre preparations obtained from tissues stored under paraffin oil, at room temperature (RT: 20-24 degrees C) and 4 degrees C for several hours. In the present study, we examined the effect of these storage conditions on the glycogen content in three muscles frequently used in research on E-C coupling: rat extensor digitorum longus (EDL) and soleus (SOL) and toad iliofibularis (IF). Glycogen content was determined fluorometrically in homogenates prepared from whole muscles, stored under paraffin oil for up to 6 h at RT or 4 degrees C. Control muscles and muscles stored for 0.5 and 6 h were also analysed for total phosphorylase (Phos(total)) and phosphorylase a (Phos a) activities. No significant change was observed in the glycogen content of EDL and SOL muscles stored at RT for 0.5 h. In rat muscles stored at RT for longer than 0.5 h, the glycogen content decreased to 67.6% (EDL) and 78.7% (SOL) of controls after 3 h and 25.3% (EDL) and 37.4% (SOL) after 6 h. Rat muscles stored at 4 degrees C retained 79.0% (EDL) and 92.5% (SOL) of glycogen after 3 h and 75.2% (EDL) and 61.1% (SOL) after 6 h. The glycogen content of IF muscles stored at RT or 4 degrees C for 6 h was not significantly different from controls. Phos(total) was unchanged in all muscles over the 6 h period, at both temperatures. Phos a was also unchanged in the toad IF muscles, but in rat muscles it decreased rapidly, particularly in EDL (4.1-fold after 0.5 h at RT). Taken together these results indicate that storage under paraffin oil for up to 6 h at RT or 4 degrees C is accompanied by minimal glycogen loss in toad IF muscles and by a time- and temperature-dependent glycogen loss in EDL and SOL muscles of the rat.

  13. Vitamin E levels in soleus muscles of experimentally induced hyperthyroid rats differ consequent to feeding of edible oils.

    PubMed

    Merican, Z; Suboh, B; Marzuki, A; Khalid, B A

    1999-12-01

    It has been shown that lipid peroxidation product levels in the soleus muscles of rats fed palm olein were lower than in the soleus muscles of rats fed soya bean oil. A study was carried out to test our hypothesis that the lower level of lipid peroxidation products in the soleus muscle of palm olein-fed rats is due, at least partly, to the higher amount of vitamin E in their soleus muscles. Experimentally induced hyperthyroid rats were fed either ground rat chow or ground rat chow mixed with palm olein oil or soya bean oil for a period of 8 weeks. Euthyroid rats fed ground rat chow for a similar period served as controls. At the end of the 8-week period, the rats were sacrificed and the α-tocopherol and tocotrienol levels in their soleus muscles were measured using high pressure liquid chromatography. It was found that the levels of α-tocopherol (23.682 ± 0.363), α-tocotrienol (1.974 ± 0.040) and γ-tocotrienol (1.418 ± 0.054) in μg/g tissue wet weight in the soleus muscles of hyperthyroid rats fed palm olein oil were statistically significantly higher than those found in the soleus muscles of hyperthyroid rats fed soya bean oil, which were 14.299 ± 0.378, 0.053 ± 0.053 and 0.184 ± 0.120μg/g tissue wet weight, respectively. The result shows that the increased level of a-tocopherol and tocotrienols found in the soleus muscles of hyperthyroid rats fed palm olein oil is responsible, at least partly, for the lower amount of lipid peroxidation products in these muscles compared with the soleus muscles of hyperthyroid rats fed soya bean oil in our earlier study.

  14. Mitochondria-targeted antioxidant preserves contractile properties and mitochondrial function of skeletal muscle in aged rats

    PubMed Central

    Javadov, Sabzali; Jang, Sehwan; Rodriguez-Reyes, Natividad; Rodriguez-Zayas, Ana E.; Hernandez, Jessica Soto; Krainz, Tanja; Wipf, Peter; Frontera, Walter

    2015-01-01

    Mitochondrial dysfunction plays a central role in the pathogenesis of sarcopenia associated with a loss of mass and activity of skeletal muscle. In addition to energy deprivation, increased mitochondrial ROS damage proteins and lipids in aged skeletal muscle. Therefore, prevention of mitochondrial ROS is important for potential therapeutic strategies to delay sarcopenia. This study elucidates the pharmacological efficiency of the new developed mitochondria-targeted ROS and electron scavenger, XJB-5-131 (XJB) to restore muscle contractility and mitochondrial function in aged skeletal muscle. Male adult (5-month old) and aged (29-month old) Fischer Brown Norway (F344/BN) rats were treated with XJB for four weeks and contractile properties of single skeletal muscle fibres and activity of mitochondrial ETC complexes were determined at the end of the treatment period. XJB-treated old rats showed higher muscle contractility associated with prevention of protein oxidation in both muscle homogenate and mitochondria compared with untreated counterparts. XJB-treated animals demonstrated a high activity of the respiratory complexes I, III, and IV with no changes in citrate synthase activity. These data demonstrate that mitochondrial ROS play a causal role in muscle weakness, and that a ROS scavenger specifically targeted to mitochondria can reverse age-related alterations of mitochondrial function and improve contractile properties in skeletal muscle. PMID:26415224

  15. Effective therapy of transected quadriceps muscle in rat: Gastric pentadecapeptide BPC 157.

    PubMed

    Staresinic, Mario; Petrovic, Igor; Novinscak, Tomislav; Jukic, Ivana; Pevec, Damira; Suknaic, Slaven; Kokic, Neven; Batelja, Lovorka; Brcic, Luka; Boban-Blagaic, Alenka; Zoric, Zdenka; Ivanovic, Domagoj; Ajduk, Marko; Sebecic, Bozidar; Patrlj, Leonardo; Sosa, Tomislav; Buljat, Gojko; Anic, Tomislav; Seiwerth, Sven; Sikiric, Predrag

    2006-05-01

    We report complete transection of major muscle and the systemic peptide treatment that induces healing of quadriceps muscle promptly and then maintains the healing with functional restoration. Initially, stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419, PL-10, PLD-116, PL 14736 Pliva, Croatia; in trials for inflammatory bowel disease; wound treatment; no toxicity reported; effective alone without carrier) also superiorly accelerates the healing of transected Achilles tendon. Regularly, quadriceps muscle completely transected transversely 1.0 cm proximal to patella presents a definitive defect that cannot be compensated in rat. BPC 157 (10 microg, 10 ng, 10 pg/kg) is given intraperitoneally, once daily; the first application 30 min posttransection, the final 24 h before sacrifice. It consistently improves muscle healing throughout the whole 72-day period. Improved are: (i) biomechanic (load of failure increased); (ii) function (walking recovery and extensor postural thrust/motor function index returned toward normal healthy values); (iii) microscopy/immunochemistry [i.e., mostly muscle fibers connect muscle segments; absent gap; significant desmin positivity for ongoing regeneration of muscle; larger myofibril diameters on both sides, distal and proximal (normal healthy rat-values reached)]; (iv) macroscopic presentation (stumps connected; subsequently, atrophy markedly attenuated; finally, presentation close to normal noninjured muscle, no postsurgery leg contracture). Thus, posttransection healing-consistently improved-may suggest this peptide therapeutic application in muscle disorders.

  16. Mitochondria-targeted antioxidant preserves contractile properties and mitochondrial function of skeletal muscle in aged rats.

    PubMed

    Javadov, Sabzali; Jang, Sehwan; Rodriguez-Reyes, Natividad; Rodriguez-Zayas, Ana E; Soto Hernandez, Jessica; Krainz, Tanja; Wipf, Peter; Frontera, Walter

    2015-11-24

    Mitochondrial dysfunction plays a central role in the pathogenesis of sarcopenia associated with a loss of mass and activity of skeletal muscle. In addition to energy deprivation, increased mitochondrial ROS damage proteins and lipids in aged skeletal muscle. Therefore, prevention of mitochondrial ROS is important for potential therapeutic strategies to delay sarcopenia. This study elucidates the pharmacological efficiency of the new developed mitochondria-targeted ROS and electron scavenger, XJB-5-131 (XJB) to restore muscle contractility and mitochondrial function in aged skeletal muscle. Male adult (5-month old) and aged (29-month old) Fischer Brown Norway (F344/BN) rats were treated with XJB for four weeks and contractile properties of single skeletal muscle fibres and activity of mitochondrial ETC complexes were determined at the end of the treatment period. XJB-treated old rats showed higher muscle contractility associated with prevention of protein oxidation in both muscle homogenate and mitochondria compared with untreated counterparts. XJB-treated animals demonstrated a high activity of the respiratory complexes I, III, and IV with no changes in citrate synthase activity. These data demonstrate that mitochondrial ROS play a causal role in muscle weakness, and that a ROS scavenger specifically targeted to mitochondria can reverse age-related alterations of mitochondrial function and improve contractile properties in skeletal muscle.

  17. Spaceflight effects on adult rat muscle protein, nucleic acids, and amino acids

    NASA Technical Reports Server (NTRS)

    Steffen, J. M.; Musacchia, X. J.

    1986-01-01

    Exposure to conditions of weightlessness has been associated with decrements in muscle mass and strength. The present studies were undertaken to determine muscle responses at the cellular level. Male Sprague-Dawley rats (360-410 g) were exposed to 7 days of weightlessness during the Spacelab-3 shuttle flight (May 1985). Animals were killed 12 h postflight, and soleus (S), gastrocnemius (G), and extensor digitorum longus (EDL) muscles were excised. Muscle protein, RNA, and DNA were extracted and quantified. Differential muscle atrophy was accompanied by a significant (P less than 0.05) reduction in total protein only in S muscles. There were no significant changes in protein concentration (mg/g) in the muscles examined. In S muscles from flight animals, sarcoplasmic protein accounted for a significantly greater proportion of total protein that in ground controls (37.5 vs. 32.5%). Tissue concentrations (nmol/g) of asparagine-aspartate, glutamine-glutamate, glycine, histidine, and lysine were significantly reduced (from 17 to 63%) in S muscles from flight animals, but only glutamine-glutamate levels were decreased in the G and EDL. Muscle DNA content (microgram) was unchanged in the tissues examined, but S muscle DNA concentration (micrograms/mg) increased 27%. RNA content (micrograms) was significantly (P less than 0.025) reduced in S (-28%) and G(-22%) muscles following spaceflight. These results identify specific alterations in rat skeletal muscle during short term (7-day) exposure to weightlessness and compare favorably with observations previously obtained from ground-based suspension simulations.

  18. The effects of Creatine Long-Term Supplementation on Muscle Morphology and Swimming Performance in Rats.

    PubMed

    Yildiz, Ahmet; Ozdemir, Ercan; Gulturk, Sefa; Erdal, Sena

    2009-01-01

    Creatine (Cr) has been shown to increase the total muscle mass. The purpose of this study was to investigate the effect of Cr supplementation on muscle morphology and swimming performance, using an animal model. Each rat was subjected to exercise 15-minute period daily for the 12 weeks. The rats were randomly divided into four groups: no Cr supplementation (CON), no Cr supplementation and incomplete food intake (lacking lysine and methionine in diet for rats) (INCO), Cr supplementation 1 g·kg(-1)·day(-1) (CREAT-I) and Cr supplementation 2 g·kg(-1)·day(-1) (CREAT-II). Three months later, all groups adult rats exercised in swimming pool chambers. Swimming time was recorded as minute for each rat. Following swimming performance period, the animals were killed by cervical dislocation and the gastrocnemius and diaphragm muscles were dissected. Serial slices of 5-7 μm were allocated paraffin wax and histochemical staining procedure of cross-sections was carried out with heamatoxylin-eosin technics. All groups gained body weight at the end of 12 weeks but there was no statistical difference among them. Swimming time values were statistical difference between CREAT-II and CON group as well as between CREAT-I and CON group (p < 0.05). In the INCO group was determined increased connective tissue cell of the muscle sample. In contrast, in the CREAT-I and CREAT-II group, the basic histological changes were large-scale muscle fibers and hypertrophic muscle cells. These results suggest that long-term creatine supplementation increased the number of muscle fibers and enhanced endurance swimming performance in rats. Key pointsThere is no study about the effects of creatine long-term supplementation on muscle morphology and swimming performance in rats.Long-term creatine supplementation increase muscle hypertrophy (but not body weight) and enhance endurance swimming performance in rats.The quantitative analysis indicated that the number of muscle fibers per defined area

  19. Muscle Is a Target for Preservation in a Rat Limb Replantation Model

    PubMed Central

    Iijima, Yuki; Teratani, Takumi; Hoshino, Yuichi; Kobayashi, Eiji

    2013-01-01

    Background: Ischemia exceeding 6 hours makes clinical limb replantation difficult and places the patient at risk of functional deficit or limb loss. We investigated the preservation of muscle function and morphology with solutions in rat hindlimb in vivo and in vitro. Methods: Quadriceps femoris muscles from luciferase transgenic rats were preserved for 24 hours at 4°C in extracellular-type trehalose containing Kyoto (ETK), University of Wisconsin (UW), or lactated Ringer’s (LR) solution (control). Muscle luminescence was measured with a bioimaging system. Amputated limbs of Lewis rats preserved with ETK, UW, or LR for 6 or 24 hours at 4°C were transplanted orthotopically. At week 8, terminal latency and amplitude were measured in the tibialis anterior muscle. The muscles were also analyzed histologically. Results: Isolated muscles preserved in ETK or UW had significantly higher luminescence than did muscles immersed in LR (P < 0.05). In the 6-hour-preserved limb transplantation model, although the 3 groups had almost the same terminal latency, electrical amplitude was significantly lower in the LR group. Histologically, muscles preserved with LR showed the most atrophic changes. In the 24-hour-preserved model, the survival rate of the LR group was 37.5% in contrast to 80% in the ETK and UW groups. Electrical signals were not detected in the LR group owing to severe muscle atrophy and fibrosis. The ETK and UW groups showed good muscle function electrophysiologically. Conclusions: Preservation solutions can protect muscle function and morphology in ischemia–reperfusion limbs and improve recipient survival rates after transplantation of long-term-preserved limbs. PMID:25289265

  20. Epigallocatechin-3-gallate improves plantaris muscle recovery after disuse in aged rats.

    PubMed

    Alway, Stephen E; Bennett, Brian T; Wilson, Joseph C; Edens, Neile K; Pereira, Suzette L

    2014-02-01

    Aging exacerbates muscle loss and slows the recovery of muscle mass and function after disuse. In this study we investigated the potential that epigallocatechin-3-gallate (EGCg), an abundant catechin in green tea, would reduce signaling for apoptosis and promote skeletal muscle recovery in the fast plantaris muscle and the slow soleus muscle after hindlimb suspension (HLS) in senescent animals. Fischer 344 × Brown Norway inbred rats (age 34 months) received either EGCg (50 mg/kg body weight), or water daily by gavage. One group of animals received HLS for 14 days and a second group of rats received 14 days of HLS, then the HLS was removed and they recovered from this forced disuse for 2 weeks. Animals that received EGCg over the HLS followed by 14 days of recovery, had a 14% greater plantaris muscle weight (p<0.05) as compared to the animals treated with the vehicle over this same period. Plantaris fiber area was greater after recovery in EGCg (2715.2±113.8 μm(2)) vs. vehicle treated animals (1953.0±41.9 μm(2)). In addition, activation of myogenic progenitor cells was improved with EGCg over vehicle treatment (7.5% vs. 6.2%) in the recovery animals. Compared to vehicle treatment, the apoptotic index was lower (0.24% vs. 0.52%), and the abundance of pro-apoptotic proteins Bax (-22%), and FADD (-77%) was lower in EGCg treated plantaris muscles after recovery. While EGCg did not prevent unloading-induced atrophy, it improved muscle recovery after the atrophic stimulus in fast plantaris muscles. However, this effect was muscle specific because EGCg had no major impact in reversing HLS-induced atrophy in the slow soleus muscle of old rats.

  1. Molecular and functional evidence for Na(+)-K(+)-2Cl(-) cotransporter expression in rat skeletal muscle.

    PubMed

    Wong, J A; Fu, L; Schneider, E G; Thomason, D B

    1999-07-01

    Doubt has been raised about the expression of a functional Na(+)-K(+)-2Cl(-) cotransporter in rat skeletal muscle. In this study we present molecular and functional evidence for expression of a protein having the characteristics of a cotransporter. RT-PCR of RNA isolated from rat soleus muscle with primers to a conserved putative membrane-spanning domain resulted in a single product of predicted size. Sequencing of the product showed that it bears >90% homology with known rodent NKCC1 (BSC2) cotransporters. RNase protection assay of RNA isolated from the rat soleus muscle also identified this sequence. Immunologic detection of the cotransporter with two different antibodies indicated the presence of cotransporter protein, perhaps more than one, in blots of total muscle protein. Immunohistochemical detection by confocal microscopy localized the majority of expression of the protein to the muscle fibers. Functional studies of cotransport activity also indicate the appropriate sensitivity to inhibitors and ion dependence. Taken together, these data support the presence and function of Na(+)-K(+)-2Cl(-) cotransporter activity in the soleus muscle of the rat.

  2. Effect of cigarette smoke exposure in vivo on bronchial smooth muscle contractility in vitro in rats.

    PubMed

    Chiba, Yoshihiko; Murata, Masahiko; Ushikubo, Hiroko; Yoshikawa, Yuji; Saitoh, Akiyoshi; Sakai, Hiroyasu; Kamei, Junzo; Misawa, Miwa

    2005-12-01

    Cigarette smoking is a risk factor for the development of airway hyperresponsiveness and chronic obstructive pulmonary disease. Little is known concerning the effect of cigarette smoking on the contractility of airway smooth muscle. The current study was performed to determine the responsiveness of bronchial smooth muscles isolated from rats that were subacutely exposed to mainstream cigarette smoke in vivo. Male Wistar rats were exposed to diluted mainstream cigarette smoke for 2 h/d every day for 2 wk. Twenty-four hours after the last cigarette smoke exposure, a marked airway inflammation (i.e., increases in numbers of neutrophils, lymphocytes, and macrophages in bronchoalveolar lavage fluid and peribronchial tissues) was observed. In these subacutely cigarette smoke-exposed animals, the responsiveness of isolated intact (nonpermeabilized) bronchial smooth muscle to acetylcholine, but not to high K+ -depolarization, was significantly augmented when compared with the air-exposed control group. In alpha-toxin-permeabilized bronchial smooth muscle strips, the acetylcholine-induced Ca2+ sensitization of contraction was significantly augmented in rats exposed to cigarette smoke, although the contraction induced by Ca2+ was control level. Immunoblot analyses revealed an increased expression of RhoA protein in the bronchial smooth muscle of rats that were exposed to cigarette smoke. Taken together, these findings suggest that the augmented agonist-induced, RhoA-mediated Ca2+ sensitization may be responsible for the enhanced bronchial smooth muscle contraction induced by cigarette smoking, which has relevance to airway hyperresponsiveness in patients with chronic obstructive pulmonary disease.

  3. [Forskolin inhibits spontaneous contraction of gastric antral smooth muscle in rats].

    PubMed

    Jiang, Jing-Zhi; Sun, Qian; Xu, Dong-Yuan; Zhang, Mo-Han; Piao, Li-Hua; Cai, Ying-Lan; Jin, Zheng

    2013-04-25

    The aim of the present study was to investigate the effects of cyclic adenosine monophosphate (cAMP) on rat gastric antral circular smooth muscle function. Forskolin, a direct activator of adenylyl cyclase (AC), was used to observe the influences of cAMP. Multi-channel physiological recorder was used to record spontaneous contraction activity of gastric antral circular muscle from Wistar rats. And ELISA method was used to detect the change of cAMP production in perfusate. The results showed that forskolin concentration-dependently suppressed the amplitude and frequency of the spontaneous contraction of the gastric antral muscle, and lowered the baseline of contraction movement significantly. Forskolin concentration-dependently increased the production of cAMP in the perfusate, which showed a significant negative correlation with the contraction amplitude of gastric antral ring muscle. The inhibitory effect of forskolin on spontaneous contraction activity of rat gastric antral circular muscle could be blocked by cAMP-dependent protein kinase (PKA) inhibitor H-89. These results suggest forskolin increases cAMP production and then activates PKA pathway, resulting in the inhibition of the spontaneous contraction activity of rat gastric antral circular smooth muscle.

  4. Identification of a skeletal muscle-specific regulatory domain in the rat GLUT4/muscle-fat gene.

    PubMed

    Richardson, J M; Pessin, J E

    1993-10-05

    To identify sequences responsible for the muscle-specific expression of the rat GLUT4/muscle-fat gene, we examined the transcriptional regulation of this gene in the differentiating murine C2C12 skeletal muscle cell line. Differentiated myofibers displayed a 4-5-fold increase in GLUT4 mRNA compared with undifferentiated myoblasts which paralleled the conversion from non-muscle beta-actin mRNA to muscle-specific alpha-actin mRNA expression. Transient transfection of progressive 5' and 3' deletions of the GLUT4 5'-flanking DNA identified a 281-base pair region located between -517 and -237 relative to the transcription start site which conferred myotube-specific expression. This region increased reporter activity in the context of the GLUT4 minimal promoter in an orientation-independent manner and, in addition, onto the heterologous thymidine kinase promoter. Myotube-specific expression of both GLUT4 reporter constructs and the endogenous mouse GLUT4 mRNA was also observed to be thyroid hormone-dependent. Further, cotransfection of reporter constructs containing the 281-base pair GLUT4 differentiation-specific enhancer with the thyroid hormone receptor specifically increased luciferase activity in myotubes approximately 12-fold. Thus, these data demonstrate the presence of a proximal skeletal muscle-specific activation domain that is necessary for both myotube-specific GLUT4 expression and thyroid hormone responsiveness.

  5. Role of afferent input and mechanical load for size regulation of rat soleus muscle

    NASA Astrophysics Data System (ADS)

    Kawano, Fuminori; Matsuka, Yoshikazu; Oke, Yoshihiko; Higo, Yoko; Terada, Masahiro; Umemoto, Shiori; Kawabe, Naoko; Wang, Xiao Dong; Shinoda, Yo; Lan, Yong Bo; Fukuda, Hiroyuki; Ohmi, Shinobu; Ohira, Yoshinobu

    2005-08-01

    Effects of deafferentation on the phosphorylation of ribosomal protein S6 (S6), 27 kDa heat shock protein (HSP27) and extracellular signal-regulated kinase (ERK) 1/2 were studied in rat soleus muscle. Adult male Wistar rats were randomly separated into the pre- and post- experimental control, functionally overloaded (FO), sham-operated, deafferentated (DA), FO+DA, and hindlimb-unloaded (U) groups. The distal tendons of left plantaris and gastrocnemius muscles were transected in the FO rats. The left dorsal roots of the spinal cord at the L4-5 segmental levels were transected in the DA rats. The rats in U were tail-suspended. The sampling of the soleus muscle was performed 2 weeks after the treatments shown above. The cytoplasmic fraction of the soleus muscle homogenate was used for the quantitative analyses of the phosphorylation levels of S6, HSP27, and ERK 1/2. The phosphorylation levels of these proteins were up-regulated by FO. On the contrary, the phosphorylation of all of these proteins was down-regulated by U and DA. Further, the FO-related increase of the protein phosphorylation was inhibited by additional treatment with DA. These results indicated that the afferent feedback plays crucial roles in the intramuscular regulation of the soleus muscle mass.

  6. Slow- and fast-twitch hindlimb skeletal muscle phenotypes 12 wk after ⅚ nephrectomy in Wistar rats of both sexes.

    PubMed

    Acevedo, Luz M; Peralta-Ramírez, Alan; López, Ignacio; Chamizo, Verónica E; Pineda, Carmen; Rodríguez-Ortiz, Maria E; Rodríguez, Mariano; Aguilera-Tejero, Escolástico; Rivero, José-Luis L

    2015-10-01

    This study describes fiber-type adaptations in hindlimb muscles, the interaction of sex, and the role of hypoxia on this response in 12-wk ⅚ nephrectomized rats (Nx). Contractile, metabolic, and morphological features of muscle fiber types were assessed in the slow-twitch soleus and the fast-twitch tibialis cranialis muscles of Nx rats, and compared with sham-operated controls. Rats of both sexes were considered in both groups. A slow-to-fast fiber-type transformation occurred in the tibialis cranialis of Nx rats, particularly in males. This adaptation was accomplished by impaired oxidative capacity and capillarity, increased glycolytic capacity, and no changes in size and nuclear density of muscle fiber types. An oxidative-to-glycolytic metabolic transformation was also found in the soleus muscle of Nx rats. However, a modest fast-to-slow fiber-type transformation, fiber hypertrophy, and nuclear proliferation were observed in soleus muscle fibers of male, but not of female, Nx rats. Serum testosterone levels decreased by 50% in male but not in female Nx rats. Hypoxia-inducible factor-1α protein level decreased by 42% in the tibialis cranialis muscle of male Nx rats. These data demonstrate that 12 wk of Nx induces a muscle-specific adaptive response in which myofibers do not change (or enlarge minimally) in size and nuclear density, but acquire markedly different contractile and metabolic characteristics, which are accompanied by capillary rarefaction. Muscle function and sex play relevant roles in these adaptations.

  7. Glucose transport and cell surface GLUT-4 protein in skeletal muscle of the obese Zucker rat.

    PubMed

    Etgen, G J; Wilson, C M; Jensen, J; Cushman, S W; Ivy, J L

    1996-08-01

    The relationship between 3-O-methyl-D-glucose transport and 2-N-4-(1-azi-2,2,2-trifluoroethyl)-benzoyl-1, 3-bis-(D-mannos-4-yloxy)-2-propylamine (ATB-BMPA)-labeled cell surface GLUT-4 protein was assessed in fast-twitch (epitrochlearis) and slow-twitch (soleus) muscles of lean and obese (fa/fa) Zucker rats. In the absence of insulin, glucose transport as well as cell surface GLUT-4 protein was similar in both epitrochlearis and soleus muscles of lean and obese rats. In contrast, insulin-stimulated glucose transport rates were significantly higher for lean than obese rats in both soleus (0.74 +/- 0.05 vs. 0.40 +/- 0.02 mumol.g-1.10 min-1) and epitrochlearis (0.51 +/- 0.05 vs. 0.17 +/- 0.02 mumol.g-1.10 min-1) muscles. The ability of insulin to enhance glucose transport in fast- and slow-twitch muscles from both lean and obese rats corresponded directly with changes in cell surface GLUT-4 protein. Muscle contraction elicited similar increases in glucose transport in lean and obese rats, with the effect being more pronounced in fast-twitch (0.70 +/- 0.07 and 0.77 +/- 0.04 mumol.g-1.10 min-1 for obese and lean, respectively) than in slow-twitch muscle (0.36 +/- 0.03 and 0.40 +/- 0.02 mumol.g-1.10 min-1 for obese and lean, respectively). The contraction-induced changes in glucose transport directly corresponded with the observed changes in cell surface GLUT-4 protein. Thus the reduced glucose transport response to insulin in skeletal muscle of the obese Zucker rat appears to result directly from an inability to effectively enhance cell surface GLUT-4 protein.

  8. Impaired Exercise Performance and Skeletal Muscle Mitochondrial Function in Rats with Secondary Carnitine Deficiency

    PubMed Central

    Bouitbir, Jamal; Haegler, Patrizia; Singh, François; Joerin, Lorenz; Felser, Andrea; Duthaler, Urs; Krähenbühl, Stephan

    2016-01-01

    Purpose: The effects of carnitine depletion upon exercise performance and skeletal muscle mitochondrial function remain largely unexplored. We therefore investigated the effect of N-trimethyl-hydrazine-3-propionate (THP), a carnitine analog inhibiting carnitine biosynthesis and renal carnitine reabsorption, on physical performance and skeletal muscle mitochondrial function in rats. Methods: Male Sprague Dawley rats were treated daily with water (control rats; n = 12) or with 20 mg/100 g body weight THP (n = 12) via oral gavage for 3 weeks. Following treatment, half of the animals of each group performed an exercise test until exhaustion. Results: Distance covered and exercise performance were lower in THP-treated compared to control rats. In the oxidative soleus muscle, carnitine depletion caused atrophy (–24%) and impaired function of complex II and IV of the mitochondrial electron transport chain. The free radical leak (ROS production relative to oxygen consumption) was increased and the cellular glutathione pool decreased. Moreover, mRNA expression of markers of mitochondrial biogenesis and mitochondrial DNA were decreased in THP-treated compared to control rats. In comparison, in the glycolytic gastrocnemius muscle, carnitine depletion was associated with impaired function of complex IV and increased free radical leak, whilst muscle weight and cellular glutathione pool were maintained. Markers of mitochondrial proliferation and mitochondrial DNA were unaffected. Conclusions: Carnitine deficiency is associated with impaired exercise capacity in rats treated with THP. THP-induced carnitine deficiency is associated with impaired function of the electron transport chain in oxidative and glycolytic muscle as well as with atrophy and decreased mitochondrial DNA in oxidative muscle. PMID:27559315

  9. Changes in skeletal muscle and tendon structure and function following genetic inactivation of myostatin in rats

    PubMed Central

    Mendias, Christopher L; Lynch, Evan B; Gumucio, Jonathan P; Flood, Michael D; Rittman, Danielle S; Van Pelt, Douglas W; Roche, Stuart M; Davis, Carol S

    2015-01-01

    Myostatin is a negative regulator of skeletal muscle and tendon mass. Myostatin deficiency has been well studied in mice, but limited data are available on how myostatin regulates the structure and function of muscles and tendons of larger animals. We hypothesized that, in comparison to wild-type (MSTN+/+) rats, rats in which zinc finger nucleases were used to genetically inactivate myostatin (MSTNΔ/Δ) would exhibit an increase in muscle mass and total force production, a reduction in specific force, an accumulation of type II fibres and a decrease and stiffening of connective tissue. Overall, the muscle and tendon phenotype of myostatin-deficient rats was markedly different from that of myostatin-deficient mice, which have impaired contractility and pathological changes to fibres and their extracellular matrix. Extensor digitorum longus and soleus muscles of MSTNΔ/Δ rats demonstrated 20–33% increases in mass, 35–45% increases in fibre number, 20–57% increases in isometric force and no differences in specific force. The insulin-like growth factor-1 pathway was activated to a greater extent in MSTNΔ/Δ muscles, but no substantial differences in atrophy-related genes were observed. Tendons of MSTNΔ/Δ rats had a 20% reduction in peak strain, with no differences in mass, peak stress or stiffness. The general morphology and gene expression patterns were similar between tendons of both genotypes. This large rodent model of myostatin deficiency did not have the negative consequences to muscle fibres and extracellular matrix observed in mouse models, and suggests that the greatest impact of myostatin in the regulation of muscle mass may not be to induce atrophy directly, but rather to block hypertrophy signalling. PMID:25640143

  10. Changes in skeletal muscle and tendon structure and function following genetic inactivation of myostatin in rats.

    PubMed

    Mendias, Christopher L; Lynch, Evan B; Gumucio, Jonathan P; Flood, Michael D; Rittman, Danielle S; Van Pelt, Douglas W; Roche, Stuart M; Davis, Carol S

    2015-04-15

    Myostatin is a negative regulator of skeletal muscle and tendon mass. Myostatin deficiency has been well studied in mice, but limited data are available on how myostatin regulates the structure and function of muscles and tendons of larger animals. We hypothesized that, in comparison to wild-type (MSTN(+/+) ) rats, rats in which zinc finger nucleases were used to genetically inactivate myostatin (MSTN(Δ/Δ) ) would exhibit an increase in muscle mass and total force production, a reduction in specific force, an accumulation of type II fibres and a decrease and stiffening of connective tissue. Overall, the muscle and tendon phenotype of myostatin-deficient rats was markedly different from that of myostatin-deficient mice, which have impaired contractility and pathological changes to fibres and their extracellular matrix. Extensor digitorum longus and soleus muscles of MSTN(Δ/Δ) rats demonstrated 20-33% increases in mass, 35-45% increases in fibre number, 20-57% increases in isometric force and no differences in specific force. The insulin-like growth factor-1 pathway was activated to a greater extent in MSTN(Δ/Δ) muscles, but no substantial differences in atrophy-related genes were observed. Tendons of MSTN(Δ/Δ) rats had a 20% reduction in peak strain, with no differences in mass, peak stress or stiffness. The general morphology and gene expression patterns were similar between tendons of both genotypes. This large rodent model of myostatin deficiency did not have the negative consequences to muscle fibres and extracellular matrix observed in mouse models, and suggests that the greatest impact of myostatin in the regulation of muscle mass may not be to induce atrophy directly, but rather to block hypertrophy signalling.

  11. Effects of microgravity on myogenic factor expressions during postnatal development of rat skeletal muscle

    NASA Technical Reports Server (NTRS)

    Inobe, Manabu; Inobe, Ikuko; Adams, Gregory R.; Baldwin, Kenneth M.; Takeda, Shin'Ichi

    2002-01-01

    To clarify the role of gravity in the postnatal development of skeletal muscle, we exposed neonatal rats at 7 days of age to microgravity. After 16 days of spaceflight, tibialis anterior, plantaris, medial gastrocnemius, and soleus muscles were removed from the hindlimb musculature and examined for the expression of MyoD-family transcription factors such as MyoD, myogenin, and MRF4. For this purpose, we established a unique semiquantitative method, based on RT-PCR, using specific primers tagged with infrared fluorescence. The relative expression of MyoD in the tibialis anterior and plantaris muscles and that of myogenin in the plantaris and soleus muscles were significantly reduced (P < 0.001) in the flight animals. In contrast, MRF4 expression was not changed in any muscle. These results suggest that MyoD and myogenin, but not MRF4, are sensitive to gravity-related stimuli in some skeletal muscles during postnatal development.

  12. Contractile properties of the rat external abdominal oblique and diaphragm muscles during development.

    PubMed

    Watchko, J F; Brozanski, B S; O'Day, T L; Guthrie, R D; Sieck, G C

    1992-04-01

    We studied the in vitro contractile and fatigue properties of the rat external abdominal oblique (EAO) and costal diaphragm (DIA) muscles during postnatal development. Isometric twitch contraction (CT) and half-relaxation (RT1/2) times were longer in both the EAO and DIA muscles during the early postnatal period and decreased with age. In the first postnatal week, the CT and RT1/2 were longer in the EAO than the DIA muscle. At 14 days of age and thereafter, the CT and RT1/2 were shorter in the EAO than in the DIA muscle. Force-frequency relationships of the EAO and DIA muscles changed during postnatal development such that the relative force (percent maximum) generated at lower frequencies (less than 15 pulses/s) decreased with age. Moreover the relative force generated by the EAO muscle at lower frequencies was greater than that of the DIA muscle during the early postnatal period but less than that of the DIA muscle in adults. The specific force of both the EAO and DIA muscles increased progressively with age. There were no differences in specific force between the EAO and DIA muscles at any age. The fatigability of the EAO and DIA muscles was comparable during the early postnatal period and increased in both muscles with postnatal development. In adults the EAO muscle was more fatigable than the DIA muscle. We conclude that the contractile and fatigue properties of the EAO and DIA muscles undergo significantly different postnatal transitions, which may reflect their functional involvement in sustaining ventilation.

  13. Increased rat neonatal activity influences adult cytokine levels and relative muscle mass

    PubMed Central

    Buchowicz, Bryce; Yu, Tiffany; Nance, Dwight M.; Zaldivar, Frank P.; Cooper, Dan M.; Adams, Gregory R.

    2011-01-01

    Little is known about the effect of physical activity in early life on subsequent growth and regulation of inflammation. We previously reported that exposure of muscles in growing rats to IL-6 results in decreased muscle growth apparently due to a state of resistance to growth factors such IGF-I and that running exercise could ameliorate this growth defect. Herein we hypothesized that increased activity, for a brief period during neonatal life, would pattern the adult rat towards a less inflammatory phenotype. Neonatal rats were induced to move about their cage for brief periods from day 5 to day 15 postpartum. Additional groups were undisturbed controls (CON) and handled (HAND). Sub-groups of rats were sampled at 30 and 65 days of age. Relative to CON and HAND, neonatal exercise (EX) results in decreased circulating levels of TNFα, IL-6 and IL-1β in adulthood, primarily in male rats. In addition, adult male EX rats had lower body mass and increased skeletal muscle mass suggesting a leaner phenotype. The results of this study suggest that moderate increases in activity early in life can influence the adult toward a more healthy phenotype with regard to inflammatory mediators and relative muscle mass. PMID:20657345

  14. Evaluation of Histological Changes in Back Muscle Injuries in Rats over Time

    PubMed Central

    Inage, Kazuhide; Sakuma, Yoshihiro; Orita, Sumihisa; Yamauchi, Kazuyo; Suzuki, Miyako; Kubota, Go; Oikawa, Yasuhiro; Sainoh, Takeshi; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Kanamoto, Hirohito; Takahashi, Kazuhisa; Ohtori, Seiji

    2017-01-01

    Study Design Animal model study. Purpose The purpose of this study was to evaluate the histological variation in the injured muscle and production of calcitonin gene-related peptide in rats over time. Overview of Literature Vertebral surgery has been reported to cause atrophy of the back muscles, which may result in pain. However, few reports have described the time series histological variation in the injured muscle and changes in the dominant nerve. Methods We used 30 male, 8-week-old Sprague-Dawley rats. The right and left sides of the paravertebral muscle were considered as the injured and uninjured sides, respectively. A 115 g weight was dropped from a height of 1 m on the right paravertebral muscle. Hematoxylin and eosin (H&E) staining of the muscle was performed 1–3 weeks after injury for histological evaluation. Fluoro-Gold (FG) was injected into the paravertebral muscle. The L2 dorsal root ganglia on both sides were resected 1, 2, and 3 weeks after injury, and immunohistochemical staining for calcitonin gene-related peptide was performed. Results H&E staining of the paravertebral muscle showed infiltration of inflammatory cells and the presence of granulation tissue in the injured part on the ipsilateral side 1 week after injury. Muscle atrophy occurred 3 weeks after injury, but was repaired via spontaneous replacement of muscle cells/fibers. In contrast, compared with the uninjured side, the percentage of cells double-labeled with FG and calcitonin gene-related peptide in FG-positive cells in the dorsal root ganglia of the injured side was significantly increased at each time point throughout the study period. Conclusions These results suggest that sensitization of the dominant nerve in the dorsal root ganglia, which may be caused by cicatrix formation, can protract injured muscle pain. This information may be helpful in elucidating the underlying mechanism of persistent pain after back muscle injury. PMID:28243375

  15. Satellite cell proliferation is reduced in muscles of obese Zucker rats but restored with loading.

    PubMed

    Peterson, Jonathan M; Bryner, Randall W; Alway, Stephen E

    2008-08-01

    The obese Zucker rat (OZR) is a model of metabolic syndrome, which has lower skeletal muscle size than the lean Zucker rat (LZR). Because satellite cells are essential for postnatal muscle growth, this study was designed to determine whether reduced satellite cell proliferation contributes to reduced skeletal mass in OZR vs. LZR. Satellite cell proliferation was determined by a constant-release 5-bromo-2-deoxyuridine (BrdU) pellet that was placed subcutaneously in each animal. Satellite cell proliferation, as determined by BrdU incorporation, was significantly attenuated in control soleus and plantaris muscles of the OZR compared with that shown in the LZR. To determine whether this attenuation of satellite cell activity could be rescued in OZR muscles, soleus and gastrocnemius muscles were denervated, placing a compensatory load on the plantaris muscle. In the LZR and the OZR after 21 days of loading, increases of approximately 25% and approximately 30%, respectively, were shown in plantaris muscle wet weight compared with that shown in the contralateral control muscle. The number of BrdU-positive nuclei increased similarly in loaded plantaris muscles from LZR and OZR. Myogenin, MyoD, and Akt protein expressions were lower in control muscles of OZR than in those of the LZR, but they were all elevated to similar levels in the loaded plantaris muscles of OZR and LZR. These data indicate that metabolic syndrome may reduce satellite cell proliferation, and this may be a factor that contributes to the reduced mass in control muscles of OZR; however, satellite cell proliferation can be restored with compensatory loading in OZR.

  16. The Effects of Phrenic Nerve Degeneration by Axotomy and Crush on the Electrical Activities of Diaphragm Muscles of Rats.

    PubMed

    Alkiş, Mehmet Eşref; Kavak, Servet; Sayır, Fuat; Him, Aydin

    2016-03-01

    The aim of this study was to investigate the effect of axotomy and crush-related degeneration on the electrical activities of diaphragm muscle strips of experimental rats. In the present study, twenty-one male Wistar-albino rats were used and divided into three groups. The animals in the first group were not crushed or axotomized and served as controls. Phrenic nerves of the rats in the second and third groups were crushed or axotomized in the diaphragm muscle. Resting membrane potential (RMP) was decreased significantly in both crush and axotomy of diaphragm muscle strips of experimental rats (p < 0.05). Depolarization time (T DEP) and half-repolarization (1/2 RT) time were significantly prolonged in crush and axotomy rats (p < 0.05). Crushing or axotomizing the phrenic nerves may produce electrical activities in the diaphragm muscle of the rat by depolarization time and half-repolarization time prolonged in crush and axotomy rats.

  17. Bradykinin B2 receptor contributes to the exaggerated muscle mechanoreflex in rats with femoral artery occlusion

    PubMed Central

    Lu, Jian; Xing, Jihong

    2013-01-01

    Static muscle contraction activates the exercise pressor reflex, which in turn increases sympathetic nerve activity (SNA) and blood pressure (BP). Bradykinin (BK) is considered as a muscle metabolite responsible for modulation of the sympathetic and cardiovascular responses to muscle contraction. Prior studies have suggested that kinin B2 receptor mediates the effects of BK on the reflex SNA and BP responses during stimulation of skeletal muscle afferents. In patients with peripheral artery disease and a rat model with femoral artery ligation, amplified SNA and BP responses to static exercise were observed. This dysfunction of the exercise pressor reflex has previously been shown to be mediated, in part, by muscle mechanoreflex overactivity. Thus, in this report, we determined whether kinin B2 receptor contributes to the augmented mechanoreflex activity in rats with 24 h of femoral artery occlusion. First, Western blot analysis was used to examine protein expression of B2 receptors in dorsal root ganglion tissues of control limbs and ligated limbs. Our data show that B2 receptor displays significant overexpression in ligated limbs as compared with control limbs (optical density: 0.94 ± 0.02 in control and 1.87 ± 0.08 after ligation, P < 0.05 vs. control; n = 6 in each group). Second, mechanoreflex was evoked by muscle stretch and the reflex renal SNA (RSNA) and mean arterial pressure (MAP) responses to muscle stretch were examined after HOE-140, a B2 receptors blocker, was injected into the arterial blood supply of the hindlimb muscles. The results demonstrate that the stretch-evoked reflex responses were attenuated by administration of HOE-140 in control rats and ligated rats; however, the attenuating effects of HOE-140 were significantly greater in ligated rats, i.e., after 5 μg/kg of HOE-140 RSNA and MAP responses evoked by 0.5 kg of muscle tension were attenuated by 43% and 25% in control vs. 54% and 34% in ligation (P < 0.05 vs. control group; n = 11 in

  18. Rat muscle plasticity in response to simulated or real microgravity.

    PubMed

    Mayet-Sornay, M H; Desplanches, D

    1996-09-01

    Data concerning muscle plasticity in real or simulated microgravity is discussed. Possible mechanisms responsible for the muscular atrophy associated with microgravity are explored, including changes in muscle protein synthesis, fast- and slow-twitch fiber specific changes, various metabolic alterations, blood supply and other factors. The authors conclude that a combination of local and systemic factors are responsible for the observed changes in muscle physiology.

  19. Induction of amino acid transporters expression by endurance exercise in rat skeletal muscle

    SciTech Connect

    Murakami, Taro Yoshinaga, Mariko

    2013-10-04

    Highlights: •Regulation of amino acid transporter expression in working muscle remains unclear. •Expression of amino acid transporters for leucine were induced by a bout of exercise. •Requirement of leucine in muscle cells might regulate expression of its transporters. •This information is beneficial for understanding the muscle remodeling by exercise. -- Abstract: We here investigated whether an acute bout of endurance exercise would induce the expression of amino acid transporters that regulate leucine transport across plasma and lysosomal membranes in rat skeletal muscle. Rats ran on a motor-driven treadmill at a speed of 28 m/min for 90 min. Immediately after the exercise, we observed that expression of mRNAs encoding L-type amino acid transporter 1 (LAT1) and CD98 was induced in the gastrocnemius, soleus, and extensor digitorum longus (EDL) muscles. Sodium-coupled neutral amino acid transporter 2 (SNAT2) mRNA was also induced by the exercise in those three muscles. Expression of proton-assisted amino acid transporter 1 (PAT1) mRNA was slightly but not significantly induced by a single bout of exercise in soleus and EDL muscles. Exercise-induced mRNA expression of these amino acid transporters appeared to be attenuated by repeated bouts of the exercise. These results suggested that the expression of amino acid transporters for leucine may be induced in response to an increase in the requirement for this amino acid in the cells of working skeletal muscles.

  20. Antihyperalgesic Effect of Tetrodotoxin in Rat Models of Persistent Muscle Pain

    PubMed Central

    Alvarez, Pedro; Levine, Jon D.

    2015-01-01

    Persistent muscle pain is a common and disabling symptom for which available treatments have limited efficacy. Since tetrodotoxin (TTX) displays a marked antinociceptive effect in models of persistent cutaneous pain, we tested its local antinociceptive effect in rat models of muscle pain induced by inflammation, ergonomic injury and chemotherapy-induced neuropathy. While local injection of TTX (0.03-1 μg) into the gastrocnemius muscle did not affect mechanical nociceptive threshold in naïve rats, exposure to the inflammogen carrageenan produced a marked muscle mechanical hyperalgesia, which was dose-dependently inhibited by TTX. This antihyperalgesic effect was still significant at 24 hours. TTX also displayed a robust antinociceptive effect on eccentric exercise-induced mechanical hyperalgesia in the gastrocnemius muscle, a model of ergonomic pain. Finally, TTX produced a small but significant inhibition of neuropathic muscle pain induced by systemic administration of the cancer chemotherapeutic agent oxaliplatin. These results indicate that TTX-sensitive sodium currents in nociceptors play a central role in diverse states of skeletal muscle nociceptive sensitization, supporting the suggestion that therapeutic interventions based on TTX may prove useful in the treatment of muscle pain. PMID:26548414

  1. Influence of 14-day hind limb unloading on isolated muscle spindle activity in rats.

    PubMed

    Zhao, Xue Hong; Fan, Xiao Li; Song, Xin Ai; Wu, Su Di; Ren, Jun Chan; Chen, Ming Xia

    2010-09-01

    During hind limb unloading (HU), the soleus is often in a shortened position and the natural physiological stimulus of muscle spindles is altered, such that muscle spindle activity also changes. Using isolated spindle conditions, the present study investigates the electrophysiological activity and ultrastructure of muscle spindles following HU. Results show that muscle spindle discharges fall into either of two main patterns, single spikes or spike clusters in shortened positions, with a steady frequency of 18-38 spikes/s (mean 29.08 +/- 2.45) in an extended position. Following 14-day HU, afferent discharge activity was significantly altered in soleus muscle spindles. Duration of individual spikes was significantly prolonged, from 0.54 +/- 0.05 ms for control rats to 1.53 +/- 0.25 ms for rats in the HU group. In a shortened position, regular rhythm afferent discharges were obviously depressed, and the majority of muscle spindles became silent, while in an extended position, the discharges remained continuous but with decreased frequency. Results also show that the ultrastructure of muscle spindles experience degenerative changes during HU. Altered muscle spindle afference could possibly modify the activity of motor neurons and further affect the activity of extrafusal fibers.

  2. Differential adaptations during growth spurt and in young adult rat muscles.

    PubMed

    Barros, K M F T; Manhaes-de-Castro, R; Goubel, F; Canon, F

    2009-01-01

    During the post-weaning growth and maturation period (25/90 days after birth), rat limb muscles are submitted to specific adaptations. Our aim was to characterize the mechanical properties of two muscles that are opposite in terms of fibre-type distribution, the soleus and the extensor digitorum longus (EDL) muscles of male Wistar rats. Results showed a fast-to-slow fibre-type transition in soleus while no modification in fibre-type distribution was observed in EDL. A growth-induced increase in muscle force was observed. Soleus underwent an increase in twitch kinetics, but EDL showed no modification. Resistance to fatigue was higher in 90-day-old soleus but not modified in the EDL. Surprisingly, analysis of maximal shortening velocity showed a decrease in both soleus and EDL. Finally, tension/extension curves indicated a growth-induced increase in series elastic stiffness in the two muscles. These results suggest that during this growth period, skeletal muscles are submitted to differential adaptations. Moreover, whereas adaptation of biomechanical properties observed can be explained partly by an adaptation of fibre profile in soleus, this is not the case for EDL. It is suggested that changes in muscle architecture, which are often disregarded, could explain some variations in mechanical properties, especially when muscles undergo an increase in both mass and length.

  3. Biomarker evaluation of skeletal muscle toxicity following clofibrate administration in rats.

    PubMed

    Bodié, Karen; Buck, Wayne R; Pieh, Julia; Liguori, Michael J; Popp, Andreas

    2016-05-01

    The use of sensitive biomarkers to monitor skeletal muscle toxicity in preclinical toxicity studies is important for the risk assessment in humans during the development of a novel compound. Skeletal muscle toxicity in Sprague Dawley Rats was induced with clofibrate at different dose levels for 7 days to compare standard clinical pathology assays with novel skeletal muscle and cardiac muscle biomarkers, gene expression and histopathological changes. The standard clinical pathology assays aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK) enzyme activity were compared to novel biomarkers fatty acid binding protein 3 (Fabp3), myosin light chain 3 (Myl3), muscular isoform of CK immunoreactivity (three isoforms CKBB, CKMM, CKMB), parvalbumin (Prv), skeletal troponin I (sTnI), cardiac troponin T (cTnT), cardiac troponin I (cTnI), CKMM, and myoglobin (Myo). The biomarker elevations were correlated to histopathological findings detected in several muscles and gene expression changes. Clofibrate predominantly induced skeletal muscle toxicity of type I fibers of low magnitude. Useful biomarkers for skeletal muscle toxicity were AST, Fabp3, Myl3, (CKMB) and sTnI. Measurements of CK enzyme activity by a standard clinical assay were not useful for monitoring clofibrate-induced skeletal muscle toxicity in the rat at the doses used in this study.

  4. Role of afferent input in load-dependent plasticity of rat muscle

    NASA Astrophysics Data System (ADS)

    Kawano, F.; Umemoto, S.; Higo, Y.; Kawabe, N.; Wang, X. D.; Lan, Y. B.; Ohira, Y.

    We have been studying the role of afferent input in the plasticity of skeletal muscles. The present study was performed to investigate the mechanisms responsible for the deafferentation-related inhibition of the compensatory hypertrophy in rat soleus muscle. Adult male Wistar rats were randomly separated into the control, functionally overloaded (FO), and functionally overloaded + deafferentation (FO+DA) group. The tendons of plantaris and gastrocnemius muscles were transected in the FO rats. The dorsal roots of the spinal cord at the L4-5 segmental levels were additionally transected in the FO+DA rats. The sampling of the soleus was performed 2 weeks after the surgery and ambulation recovery. The single muscle fibers were isolated in low-calcium relaxing solution. Further, the myonuclei or argyrophilic nucleolar organizer regions (AgNORs) were stained. Significant increase of the fiber cross-sectional area (CSA) was seen in the FO, but not in the FO+DA, rats. The myonuclear number in fiber was significantly decreased by FO. Addition of DA to FO further promoted the reduction of myonuclear number. The mean nucleus size and DNA content in single nucleus in all groups were identical. Although a single or double AgNORs were seen in ~90% of myonuclei in the control rats, their distributions were 72 and 76% in the FO and FO+DA rats, respectively (p<0.05). More myonuclei containing 3-5 AgNORs were noted in the FO and FO+DA rats. The mean number of the AgNORs per myonucleus was 1.7 in the control, 2.1 in both FO and FO+DA rats (p<0.05). It was suggested that the FO-related increase of the number of AgNORs may be responsible for the induction of compensatory hypertrophy. It was also indicated that intact afferent input plays an essential role in these phenomena.

  5. Effects of age on aneural regeneration of soleus muscle in rat.

    PubMed Central

    Lewis, D M; Schmalbruch, H

    1995-01-01

    1. The ability of autografted soleus muscles to regenerate without innervation was investigated in young (two groups: 17 days or 35 g and 5 weeks or 100 g) and old (10 weeks or 300 g and 19 months or 700 g) rats. 2. Tetanic force and fibre area of the regenerated muscles were followed in 35, 100 and 300 g rats and found to reach a maximum 10-15 days after the operation and then declined. 3. Maximal tetanic force and fibre area were greater in old than in young rats; the largest increase was seen between 100 and 300 g rats. The relaxation phase of the twitch became shorter in the 700 g animals. The force per cross-sectional area appeared to fall with age. The length of the new fibres, inferred from the width of the length-force curve, increased only slightly with age. 4. Ten days after grafting, autophagocytosis of necrotic fibres was completed in young but not in old rats. The new fibres in young rats had one central nucleus per cross-section and fibre size was unimodally distributed; fibres in old rats had multiple internal nuclei and the size distribution was bimodal due to the presence of large fibres. 5. Previous results indicating greater muscle regeneration in young than in old rats may reflect more vigorous reinnervation in young animals rather than a greater myogenic potential. Increased fibre size of regenerated muscles of old compared with young rats may be attributed to the larger amount of necrotic material which is mitogenic for satellite cells, or to age-dependent changes of the expression of cell adhesion molecules. Enhanced lateral fusion of myotubes would give rise to large fibres with multiple internal nuclei. Images Figure 3 Figure 4 PMID:8568686

  6. Contractile properties of rat fast-twitch skeletal muscle during reinnervation - Effects of testosterone and castration

    NASA Technical Reports Server (NTRS)

    Yeagle, S. P.; Mayer, R. F.; Max, S. R.

    1983-01-01

    The peroneal nerve of subject rats were crushed 1 cm from the muscle in order to examine the isometric contractile properties of skeletal muscle in the recovery sequency during reinnervation of normal, castrated, and testosterone-treated rats. The particular muscle studied was the extensor digitorum longus, with functional reinnervation first observed 8-9 days after nerve crush. No evidence was found that either castration or testosterone injections altered the process of reinnervation after the nerve crush, with the conclusion being valid at the 0.05 p level. The most reliable index of reinnervation was found to be the twitch:tetanus ratio, a factor of use in future studies of the reinnervation of skeletal muscle.

  7. Activation of the ATP-ubiquitin-proteasome pathway in skeletal muscle of cachectic rats bearing a hepatoma

    NASA Technical Reports Server (NTRS)

    Baracos, V. E.; DeVivo, C.; Hoyle, D. H.; Goldberg, A. L.

    1995-01-01

    Rats implanted with Yoshida ascites hepatoma (YAH) show a rapid and selective loss of muscle protein due mainly to a marked increase (63-95%) in the rate of protein degradation (compared with rates in muscles of pair-fed controls). To define which proteolytic pathways contribute to this increase, epitrochlearis muscles from YAH-bearing and control rats were incubated under conditions that modify different proteolytic systems. Overall proteolysis in either group of rats was not affected by removal of Ca2+ or by blocking the Ca(2+)-dependent proteolytic system. Inhibition of lysosomal function with methylamine reduced proteolysis (-12%) in muscles from YAH-bearing rats, but not in muscles of pair-fed rats. When ATP production was also inhibited, the remaining accelerated proteolysis in muscles of tumor-bearing rats fell to control levels. Muscles of YAH-bearing rats showed increased levels of ubiquitin-conjugated proteins and a 27-kDa proteasome subunit in Western blot analysis. Levels of mRNA encoding components of proteolytic systems were quantitated using Northern hybridization analysis. Although their total RNA content decreased 20-38%, pale muscles of YAH-bearing rats showed increased levels of ubiquitin mRNA (590-880%) and mRNA for multiple subunits of the proteasome (100-215%). Liver, kidney, heart, and brain showed no weight loss and no change in these mRNA species. Muscles of YAH-bearing rats also showed small increases (30-40%) in mRNA for cathepsins B and D, but not for calpain I or heat shock protein 70. Our findings suggest that accelerated muscle proteolysis and muscle wasting in tumor-bearing rats result primarily from activation of the ATP-dependent pathway involving ubiquitin and the proteasome.

  8. Skeletal muscle fiber, nerve, and blood vessel breakdown in space-flown rats

    NASA Technical Reports Server (NTRS)

    Riley, D. A.; Ilyina-Kakueva, E. I.; Ellis, S.; Bain, J. L.; Slocum, G. R.; Sedlak, F. R.

    1990-01-01

    Histochemical and ultrastructural analyses were performed postflight on hind limb skeletal muscles of rats orbited for 12.5 days aboard the unmanned Cosmos 1887 biosatellite and returned to Earth 2 days before sacrifice. The antigravity adductor longus (AL), soleus, and plantaris muscles atrophied more than the non-weight-bearing extensor digitorum longus, and slow muscle fibers were more atrophic than fast fibers. Muscle fiber segmental necrosis occurred selectively in the AL and soleus muscles; primarily, macrophages and neutrophils infiltrated and phagocytosed cellular debris. Granule-rich mast cells were diminished in flight AL muscles compared with controls, indicating the mast cell secretion contributed to interstitial tissue edema. Increased ubiquitination of disrupted myofibrils implicated ubiquitin in myofilament degradation. Mitochondrial content and succinic dehydrogenase activity were normal, except for subsarcolemmal decreases. Myofibrillar ATPase activity of flight AL muscle fibers shifted toward the fast type. Absence of capillaries and extravasation of red blood cells indicated failed microcirculation. Muscle fiber regeneration from activated satellite cells was detected. About 17% of the flight AL end plates exhibited total or partial denervation. Thus, skeletal muscle weakness associated with spaceflight can result from muscle fiber atrophy and segmental necrosis, partial motor denervation, and disruption of the microcirculation.

  9. Adaptation of rat soleus muscles to 4 wk of intermittent strain

    NASA Technical Reports Server (NTRS)

    Stauber, W. T.; Miller, G. R.; Grimmett, J. G.; Knack, K. K.

    1994-01-01

    The effect of repeated strains on rat soleus muscles was investigated by stretching active muscles 3 times/wk for 4 wk with two different methods of stretching. The adaptation of myofibers and noncontractile tissue was followed by histochemical techniques and computer-assisted image analysis. Muscle hypertrophy was seen in the slow-stretched muscles, which increased in mass by 13% and increased in myofiber cross-sectional area by 30%. In the fast-stretched muscle, mass increased by 10% but myofiber cross-sectional area actually decreased. This decrease in mean fiber area was the result of a population of very small fibers (population A) that coexisted with slightly smaller normal-sized fibers (population B). Fibers in population A did not have the distribution expected from atrophy compared with atrophic fibers from unloaded muscles; they were much smaller. In addition, there was a 44% increase in noncontractile tissue in the fast-stretched muscles. Thus, soleus muscles subjected to repeated strains respond differently to slow and fast stretching. Slow stretching results in typical muscle hypertrophy, whereas fast stretching produces somewhat larger muscles but with a mixture of small and normal-sized myofibers accompanied by a marked proliferation of noncontractile tissue.

  10. Hindlimb unloading induces a collagen isoform shift in the soleus muscle of the rat

    NASA Technical Reports Server (NTRS)

    Miller, T. A.; Lesniewski, L. A.; Muller-Delp, J. M.; Majors, A. K.; Scalise, D.; Delp, M. D.

    2001-01-01

    To determine whether hindlimb unloading (HU) alters the extracellular matrix of skeletal muscle, male Sprague-Dawley rats were subjected to 0 (n = 11), 1 (n = 11), 14 (n = 13), or 28 (n = 11) days of unloading. Remodeling of the soleus and plantaris muscles was examined biochemically for collagen abundance via measurement of hydroxyproline, and the percentage of cross-sectional area of collagen was determined histologically with picrosirius red staining. Total hydroxyproline content in the soleus and plantaris muscles was unaltered by HU at any time point. However, the relative proportions of type I collagen in the soleus muscle decreased relative to control (Con) with 14 and 28 days HU (Con 68 +/- 5%; 14 days HU 53 +/- 4%; 28 days HU 53 +/- 7%). Correspondingly, type III collagen increased in soleus muscle with 14 and 28 days HU (Con 32 +/- 5%; 14 days HU 47 +/- 4%; 28 days HU 48 +/- 7%). The proportion of type I muscle fibers in soleus muscle was diminished with HU (Con 96 +/- 2%; 14 days HU 86 +/- 1%; 28 days HU 83 +/- 1%), and the proportion of hybrid type I/IIB fibers increased (Con 0%; 14 days HU 8 +/- 2%; 28 days HU 14 +/- 2%). HU had no effect on the proportion of type I and III collagen or muscle fiber composition in plantaris muscle. The data demonstrate that HU induces a shift in the relative proportion of collagen isoform (type I to III) in the antigravity soleus muscle, which occurs concomitantly with a slow-to-fast myofiber transformation.

  11. Overload-induced skeletal muscle hypertrophy is not impaired in STZ-diabetic rats

    PubMed Central

    Fortes, Marco Aurélio S; Pinheiro, Carlos Hermano J; Guimarães-Ferreira, Lucas; Vitzel, Kaio F; Vasconcelos, Diogo A A; Curi, Rui

    2015-01-01

    The aim of this study was to evaluate the effect of overload-induced hypertrophy on extensor digitorum longus (EDL) and soleus muscles of streptozotocin-induced diabetic rats. The overload-induced hypertrophy and absolute tetanic and twitch forces increases in EDL and soleus muscles were not different between diabetic and control rats. Phospho-Akt and rpS6 contents were increased in EDL muscle after 7 days of overload and returned to the pre-overload values after 30 days. In the soleus muscle, the contents of total and phospho-Akt and total rpS6 were increased in both groups after 7 days. The contents of total Akt in controls and total rpS6 and phospho-Akt in the diabetic rats remained increased after 30 days. mRNA expression after 7 days of overload in the EDL muscle of control and diabetic animals showed an increase in MGF and follistatin and a decrease in myostatin and Axin2. The expression of FAK was increased and of MuRF-1 and atrogin-1 decreased only in the control group, whereas Ankrd2 expression was enhanced only in diabetic rats. In the soleus muscle caused similar changes in both groups: increase in FAK and MGF and decrease in Wnt7a, MuRF-1, atrogin-1, and myostatin. Differences between groups were observed only in the increased expression of follistatin in diabetic animals and decreased Ankrd2 expression in the control group. So, insulin deficiency does not impair the overload-induced hypertrophic response in soleus and EDL muscles. However, different mechanisms seem to be involved in the comparable hypertrophic responses of skeletal muscle in control and diabetic animals. PMID:26197932

  12. Dexmedetomidine ameliorates muscle wasting and attenuates the alteration of hypothalamic neuropeptides and inflammation in endotoxemic rats

    PubMed Central

    Cheng, Minhua; Gao, Tao; Xi, Fengchan; Cao, Chun; Chen, Yan; Zhao, Chenyan; Li, Qiurong

    2017-01-01

    Dexmedetomidine is generally used for sedaton in critically ill, it could shorten duration of mechanical ventilation, ICU stay and lower basic metabolism. However, the exact mechanism of these positive effects remains unkown. Here we investigated the hypothesis that dexmedetomidine could ameliorate muscle wasting in endotoxemic rats and whether it was related to hypothalamic neuropeptides alteration and inflammation. Fourty-eight adult male Sprague–Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) (5 mg/kg) or saline, followed by 50 μg/kg dexmedetomidine or saline administration via the femoral vein catheter (infusion at 5 μg·kg-1·hr-1). Twenty-four hours after injection, hypothalamus tissues and skeletal muscle were obtained. Muscle wasting was measured by the mRNA expression of two E3 ubiquitin ligases, muscle atrophy F-box (MAFbx) and muscle ring finger 1 (MuRF-1) as well as 3-methylhistidine (3-MH) and tyrosine release. Hypothalamic inflammatory markers and neuropeptides expression were also detected in all four groups. Results showed that LPS administration led to significant increase in hypothalamic inflammation together with muscle wasting. Increased hypothalamic neuropeptides, proopiomelanocortin (POMC), cocaine and amphetamine-related transcript (CART) and neuropeptides Y (NPY) and decreased agouti-related protein (AgRP) were also observed. Meanwhile dexmedetomidine administration ameliorated muscle wasting, hypothalamic inflammation and modulated the alteration of neuropeptides, POMC, CART and AgRP, in endotoxemic rats. In conclusion, dexmedetomidine could alleviate muscle wasting in endotoxemic rats, and it could also attenuate the alteration of hypothalamic neuropeptides and reduce hypothalamic inflammation. PMID:28358856

  13. Overload-induced skeletal muscle hypertrophy is not impaired in STZ-diabetic rats.

    PubMed

    Fortes, Marco Aurélio S; Pinheiro, Carlos Hermano J; Guimarães-Ferreira, Lucas; Vitzel, Kaio F; Vasconcelos, Diogo A A; Curi, Rui

    2015-07-01

    The aim of this study was to evaluate the effect of overload-induced hypertrophy on extensor digitorum longus (EDL) and soleus muscles of streptozotocin-induced diabetic rats. The overload-induced hypertrophy and absolute tetanic and twitch forces increases in EDL and soleus muscles were not different between diabetic and control rats. Phospho-Akt and rpS6 contents were increased in EDL muscle after 7 days of overload and returned to the pre-overload values after 30 days. In the soleus muscle, the contents of total and phospho-Akt and total rpS6 were increased in both groups after 7 days. The contents of total Akt in controls and total rpS6 and phospho-Akt in the diabetic rats remained increased after 30 days. mRNA expression after 7 days of overload in the EDL muscle of control and diabetic animals showed an increase in MGF and follistatin and a decrease in myostatin and Axin2. The expression of FAK was increased and of MuRF-1 and atrogin-1 decreased only in the control group, whereas Ankrd2 expression was enhanced only in diabetic rats. In the soleus muscle caused similar changes in both groups: increase in FAK and MGF and decrease in Wnt7a, MuRF-1, atrogin-1, and myostatin. Differences between groups were observed only in the increased expression of follistatin in diabetic animals and decreased Ankrd2 expression in the control group. So, insulin deficiency does not impair the overload-induced hypertrophic response in soleus and EDL muscles. However, different mechanisms seem to be involved in the comparable hypertrophic responses of skeletal muscle in control and diabetic animals.

  14. Alteration of gene expression profiles in skeletal muscle of rats exposed to microgravity during a spaceflight

    NASA Technical Reports Server (NTRS)

    Taylor, Wayne E.; Bhasin, Shalender; Lalani, Rukhsana; Datta, Anuj; Gonzalez-Cadavid, Nestor F.

    2002-01-01

    To clarify the mechanism of skeletal muscle wasting during spaceflights, we investigated whether intramuscular gene expression profiles are affected, by using DNA microarray methods. Male rats sent on the 17-day NASA STS-90 Neurolab spaceflight were sacrificed 24 hours after return to earth (MG group). Ground control rats were maintained for 17 days in flight-simulated cages (CS group). Spaceflight induced a 19% and 23% loss of tibialis anterior and gastrocnemius muscle mass, respectively, as compared to ground controls. Muscle RNA was analyzed by the Clontech Atlas DNA expression array in four rats, with two MG/ CS pairs for the tibialis anterior, and one pair for the gastrocnemius. Alterations in gene expression were verified for selected genes by reverse-transcription PCR. In both muscles of MG rats, mRNAs for 12 genes were up-regulated by over 2-fold, and 38 were down-regulated compared to controls. There was inhibition of genes for cell proliferation and growth factor cascades, including cell cycle genes and signal transduction proteins, such as p21 Cip1, retinoblastoma (Rb), cyclins G1/S, -E and -D3, MAP kinase 3, MAD3, and ras related protein RAB2. These data indicate that following exposure to microgravity, there is downregulation of genes involved in regulation of muscle satellite cell replication.

  15. Skeletal muscle afferent regulation of bioassayable growth hormone in the rat pituitary

    NASA Technical Reports Server (NTRS)

    Gosselink, K. L.; Grindeland, R. E.; Roy, R. R.; Zhong, H.; Bigbee, A. J.; Grossman, E. J.; Edgerton, V. R.

    1998-01-01

    There are forms of growth hormone (GH) in the plasma and pituitary of the rat and in the plasma of humans that are undetected by presently available immunoassays (iGH) but can be measured by bioassay (bGH). Although the regulation of iGH release is well documented, the mechanism(s) of bGH release is unclear. On the basis of changes in bGH and iGH secretion in rats that had been exposed to microgravity conditions, we hypothesized that neural afferents play a role in regulating the release of these hormones. To examine whether bGH secretion can be modulated by afferent input from skeletal muscle, the proximal or distal ends of severed hindlimb fast muscle nerves were stimulated ( approximately 2 times threshold) in anesthetized rats. Plasma bGH increased approximately 250%, and pituitary bGH decreased approximately 60% after proximal nerve trunk stimulation. The bGH response was independent of muscle mass or whether the muscles were flexors or extensors. Distal nerve stimulation had little or no effect on plasma or pituitary bGH. Plasma iGH concentrations were unchanged after proximal nerve stimulation. Although there may be multiple regulatory mechanisms of bGH, the present results demonstrate that the activation of low-threshold afferents from fast skeletal muscles can play a regulatory role in the release of bGH, but not iGH, from the pituitary in anesthetized rats.

  16. Enhanced skeletal muscle insulin sensitivity in year-old rats adapted to hypergravity

    NASA Technical Reports Server (NTRS)

    Mondon, C. E.; Dolkas, C. B.; Oyama, J.

    1981-01-01

    Rats induced into a hypermetabolic state by exposure to chronic (7 mo) centrifugation at 4.15 g exhibited increased glucose uptake at lower plasma insulin levels than weight-matched control animals following oral glucose administration. In order to determine the insulin sensitivity of specific tissues, the effect of exogenous insulin on glucose uptake by isolated perfused livers and hindlim skeletal muscle from rats adapted to chronic centrifugation for one year was compared with perfused tissue from 2.5 mo-old noncentrifuged control animals of equal body weight. Metabolic glucose clearance by skeletal muscle from hypergravic rats did not prove significantly greater than control muscle when perfused in the absence of insulin (10.6 vs 8.1 microliters/min-g-muscle), but was twice as fast (23.0 vs 9.5) at perfusate insulin levels of 35 micro-U/ml. Conversely, glucose uptake by hypergravic livers was significantly decreased (P is less than 0.001) compared with control livers (10.3 vs 27.8) at perfusate insulin levels of 40 micro-U/ml. Results suggest that skeletal muscle rather than liver is primarily responsible for the enhanced sensitivity to insulin and the increased energy expenditure observed in rats subjected to hypergravity.

  17. Longitudinal and transversal displacements between triceps surae muscles during locomotion of the rat.

    PubMed

    Bernabei, Michel; van Dieën, Jaap H; Maas, Huub

    2017-02-15

    The functional consequences of differential muscle activation and contractile behavior between mechanically coupled synergists are still poorly understood. Even though synergistic muscles exert similar mechanical effects at the joint they span, differences in the anatomy, morphology and neural drive may lead to non-uniform contractile conditions. This study aimed to investigate the patterns of activation and contractile behavior of triceps surae muscles, to understand how these contribute to the relative displacement between the one-joint soleus (SO) and two-joint lateral gastrocnemius (LG) muscle bellies and their distal tendons during locomotion in the rat. In seven rats, muscle belly lengths and muscle activation during level and upslope trotting were measured by sonomicrometry crystals and electromyographic electrodes chronically implanted in the SO and LG. Length changes of muscle-tendon units (MTUs) and tendon fascicles were estimated based on joint kinematics and muscle belly lengths. Distances between implanted crystals were further used to assess longitudinal and transversal deformations of the intermuscular volume between the SO and LG. For both slope conditions, we observed differential timing of muscle activation as well as substantial differences in contraction speeds between muscle bellies (maximal relative speed 55.9 mm s(-1)). Muscle lengths and velocities did not differ significantly between level and upslope locomotion, only EMG amplitude of the LG was affected by slope. Relative displacements between SO and LG MTUs were found in both longitudinal and transversal directions, yielding an estimated maximal length change difference of 2.0 mm between their distal tendons. Such relative displacements may have implications for the force exchanged via intermuscular and intertendinous pathways.

  18. Metabolic alterations caused by suspension hypokinesia in leg muscles of rats

    NASA Technical Reports Server (NTRS)

    Tischler, M. E.

    1984-01-01

    Metabolic changes on hypokinetic rats were measured. Two groups of animals were studied: (1) weight bearing control which were tail casted but allowed to walk on all four limbs, and (2) hypokinetic with no load bearing of the hindlimbs. The control and hypokinetic rats gained weight at a steady and similar rate over 6 days. Hypokinesia for 6 days led to significantly lower relative weights of the soleus, gastrocnemius and plantaris muscles. Hypokinesia did not effect the relative mass of the anterior tibialis or extensor digitorum longus (EDL) muscles.

  19. Synthesis of amino acids in weight bearing and non-weight bearing leg muscles of suspended rats

    NASA Technical Reports Server (NTRS)

    Tischler, M. E.; Jaspers, S. R.

    1982-01-01

    The effect of hypokinesia (HYP) for 6 days on the de novo synthesis of glutamine (GLN) and glutamate (GLU), and of alanine was tested in isolated leg muscles of intact, adrenalectomized (ADX) and ADX cortisol-treated rats. The net synthesis of GLN and GLU was lower in soleus muscles of HYP animals of these three groups of rats. The synthesis of alanine was lowered by HYP in ADX animals and apparently raised by HYP in ADX cortisol-treated rats. No HYP effect was seen in the extensor digitorum longus (EDL) muscles of these animals. Although ADX lowered the synthesis of GLN and GLU in soleus muscles of control rats, while cortisol treatment restored this process to near normal, neither ADX nor cortisol treatment produced any effect in the HYP animals. However, effects of ADX and cortisol treatment on synthesis of GLN and GLU in EDL muscles and of alanine in both muscles seemed normal in HYP animals.

  20. Oxidative stress participates in quadriceps muscle dysfunction during the initiation of osteoarthritis in rats.

    PubMed

    Hsu, Dur-Zong; Chu, Pei-Yi; Wu, Po-Ting; Shen, Po-Chuan; Jou, I-Ming

    2015-01-01

    Osteoarthritis is the most common form of arthritis, affecting approximately 15% of the population. Quadriceps muscle weakness is one of the risk factors of osteoarthritis development. Oxidative stress has been reported to play an important role in the pathogenesis of various muscle dysfunction; however, whether it is involved in osteoarthritis-associated quadriceps muscle weakness has never been investigated. The aim of the present study is to examine the involvement of oxidative stress in quadriceps muscle dysfunction in the initiation of osteoarthritis in rats. Rat osteoarthritis was initiated by conducting meniscectomy (MNX). Quadriceps muscle dysfunction was evaluated by assessing muscular interleukin-6, citrate synthase activity, and myosin heavy chain IIa mRNA expression levels. Muscular oxidative stress was assessed by determining lipid peroxidation, Nrf2 expression, reactive oxygen species, and circulating antioxidants. Increased muscular interleukin-6 production as well as decreased citrate synthase activity and myosin heavy chain IIa mRNA expression were observed at 7 and 14 days after MNX. Biomarkers of oxidative stress were significantly increased after MNX. Muscular free radical counts were increased while glutathione and glutathione peroxidase expression were decreased in MNX-treated rats. We conclude that oxidative stress may be involved in the pathogenesis of muscle dysfunction in MNX-induced osteoarthritis.

  1. IB4-Saporin Attenuates Acute and Eliminates Chronic Muscle Pain in the Rat

    PubMed Central

    Alvarez, Pedro; Gear, Robert W.; Green, Paul G.; Levine, Jon D.

    2012-01-01

    The function of populations of nociceptors in muscle pain syndromes remain poorly understood. We compared the contribution of two major classes, isolectin B4-positive (IB4(+)) and IB4-negative (IB4(−)) nociceptors, in acute and chronic inflammatory and ergonomic muscle pain. Baseline mechanical nociceptive threshold was assessed in the gastrocnemius muscle of rats treated with IB4-saporin, which selectively destroys IB4(+) nociceptors. Rats were then submitted to models of acute inflammatory (intramuscular carrageenan)- or ergonomic intervention (eccentric exercise or vibration)-induced muscle pain, and each of the three models also evaluated for the transition from acute to chronic pain, manifest as prolongation of prostaglandin E2 (PGE2)-induced hyperalgesia, after recovery from the hyperalgesia induced by acute inflammation or ergonomic interventions. IB4-saporin treatment did not affect baseline mechanical nociceptive threshold. However, compared to controls, IB4-saporin treated rats exhibited shorter duration mechanical hyperalgesia in all three models and attenuated peak hyperalgesia in the ergonomic pain models. And, IB4-saporin treatment completely prevented prolongation of PGE2-induced mechanical hyperalgesia. Thus, IB4(+) and IB4(−) neurons contribute to acute muscle hyperalgesia induced by diverse insults. However, only IB4+ nociceptors participate in the long term consequence of acute hyperalgesia. Finally, using retrograde labelling we found that approximately 70% of sensory neurons innervating the gastrocnemius muscle are IB4(+). PMID:22206923

  2. Androgen-estrogen synergy in rat levator ani muscle Glucose-6-phosphate dehydrogenase

    NASA Technical Reports Server (NTRS)

    Max, S. R.

    1984-01-01

    The effects of castration and hormone administration on the activity of glucose-6-phosphate dehydrogenase in the rat levator ani muscle were studied. Castration caused a decrease in enzyme activity and in wet weight of the levator ani muscle. Chronic administration of testosterone propionate increased glucose-6-phosphate dehydrogenase activity in the levator ani muscle of castrated rats; the magnitude of the recovery of enzyme activity was related to the length of time of exposure to testosterone propionate after castration as well as to the length of time the animals were castrated. The longer the period of castration before exposure to testosterone propionate, the greater the effect. This result may be related to previously reported castration-mediated increases in androgen receptor binding in muscle. Dihydrotestosterone was less effective than testosterone propionate in enhancing glucose-6-phosphate dehydrogenase activity in the levator ani muscle from castrated rats; estradiol-17-beta alone was ineffective. Combined treatment with estradiol-17-beta and dihydrotestosterone, however, was as effective as testosterone alone. Thus, androgens and estrogens may exert synergistic effects on levator ani muscle.

  3. Imbalance in SOD/CAT activities in rat skeletal muscles submitted to treadmill training exercise.

    PubMed

    Pinho, Ricardo A; Andrades, Michael E; Oliveira, Marcos R; Pirola, Aline C; Zago, Morgana S; Silveira, Paulo C L; Dal-Pizzol, Felipe; Moreira, José Cláudio F

    2006-10-01

    The association between physical exercise and oxidative damage in the skeletal musculature has been the focus of many studies in literature, but the balance between superoxide dismutase and catalase activities and its relation to oxidative damage is not well established. Thus, the aim of the present study was to investigate the association between regular treadmill physical exercise, oxidative damage and antioxidant defenses in skeletal muscle of rats. Fifteen male Wistar rats (8-12 months) were randomly separated into two groups (trained n=9 and untrained n=6). Trained rats were treadmill-trained for 12 weeks in progressive exercise (velocity, time, and inclination). Training program consisted in a progressive exercise (10 m/min without inclination for 10 min/day). After 1 week the speed, time and inclination were gradually increased until 17 m/min at 10% for 50 min/day. After the training period animals were killed, and gastrocnemius and quadriceps were surgically removed to the determination of biochemical parameters. Lipid peroxidation, protein oxidative damage, catalase, superoxide dismutase and citrate synthase activities, and muscular glycogen content were measured in the isolated muscles. We demonstrated that there is a different modulation of CAT and SOD in skeletal muscle in trained rats when compared to untrained rats (increased SOD/CAT ratio). TBARS levels were significantly decreased and, in contrast, a significant increase in protein carbonylation was observed. These results suggest a non-described adaptation of skeletal muscle against exercise-induced oxidative stress.

  4. Metabolic and morphologic properties of single muscle fibers in the rat after spaceflight, Cosmos 1887

    NASA Technical Reports Server (NTRS)

    Miu, B.; Martin, T. P.; Roy, R. R.; Oganov, V.; Ilyina-Kakueva, E.; Marini, J. F.; Leger, J. J.; Bodine-Fowler, S. C.; Edgerton, V. R.

    1990-01-01

    The adaptation of a slow (soleus, Sol) and a fast (medial gastrocnemius, MG) skeletal muscle to spaceflight was studied in five young male rats. The flight period was 12.5 days and the rats were killed approximately 48 h after returning to 1 g. Five other rats that were housed in cages similar to those used by the flight rats were maintained at 1 g for the same period of time to serve as ground-based controls. Fibers were classified as dark or light staining for myosin adenosine triphosphatase (ATPase). On the average, the fibers in the Sol of the flight rats atrophied twice as much as those in the MG. Further, the fibers located in the deep (close to the bone and having the highest percentage of light ATPase and high oxidative fibers in the muscle cross section) region of the MG atrophied more than the fibers located in the superficial (away from the bone and having the lowest percentage of light ATPase and high oxidative fibers in the muscle cross-section) region of the muscle. Based on quantitative histochemical assays of single muscle fibers, succinate dehydrogenase (SDH) activity per unit volume was unchanged in fibers of the Sol and MG. However, in the Sol, but not the MG, the total amount of SDH activity in a 10-microns-thick section of a fiber decreased significantly in response to spaceflight. Based on population distributions, it appears that the alpha-glycerophosphate dehydrogenase (GPD) activities were elevated in the dark ATPase fibers in the Sol, whereas the light fibers in the Sol and both fiber types in the MG did not appear to change. The ratio of GPD to SDH activities increased in the dark (but not light) fibers of the Sol and was unaffected in the MG. Immunohistochemical analyses indicate that approximately 40% of the fibers in the Sol of flight rats expressed a fast myosin heavy chain compared with 22% in control rats. Further, 31% of the fibers in the Sol of flight rats expressed both fast and slow myosin heavy chains compared with 8% in

  5. Effects of alkali supplementation and vitamin D insufficiency on rat skeletal muscle.

    PubMed

    Ceglia, Lisa; Rivas, Donato A; Pojednic, Rachele M; Price, Lori Lyn; Harris, Susan S; Smith, Donald; Fielding, Roger A; Dawson-Hughes, Bess

    2013-10-01

    Data on the independent and potential combined effects of acid-base balance and vitamin D status on muscle mass and metabolism are lacking. We investigated whether alkali supplementation with potassium bicarbonate (KHCO3), with or without vitamin D3 (± VD3), alters urinary nitrogen (indicator of muscle proteolysis), muscle fiber cross-sectional area (FCSA), fiber number (FN), and anabolic (IGF-1, Akt, p70s6k) and catabolic (FOXO3a, MURF1, MAFbx) signaling pathways regulating muscle mass. Thirty-six, 20-month-old, Fischer 344/Brown-Norway rats were randomly assigned in a 2 × 2 factorial design to one of two KHCO3-supplemented diets (± VD3) or diets without KHCO3 (± VD3) for 12 weeks. Soleus, extensor digitorum longus (EDL), and plantaris muscles were harvested at 12 weeks. Independent of VD3 group, KHCO3 supplementation resulted in 35 % lower mean urinary nitrogen to creatinine ratio, 10 % higher mean type I FCSA (adjusted to muscle weight), but no statistically different mean type II FCSA (adjusted to muscle weight) or FN compared to no KHCO3. Among VD3-replete rats, phosphorylated-Akt protein expression was twofold higher in the KHCO3 compared to no KHCO3 groups, but this effect was blunted in rats on VD3-deficient diets. Neither intervention significantly affected serum or intramuscular IGF-1 expression, p70s6k or FOXO3a activation, or MURF1 and MAFbx gene expression. These findings provide support for alkali supplementation as a promising intervention to promote preservation of skeletal muscle mass, particularly in the setting of higher vitamin D status. Additional research is needed in defining the muscle biological pathways that are being targeted by alkali and vitamin D supplementation.

  6. Temporal changes in sarcomere lesions of rat adductor longus muscles during hindlimb reloading

    NASA Technical Reports Server (NTRS)

    Krippendorf, B. B.; Riley, D. A.

    1994-01-01

    Focal sarcomere disruptions were previously observed in adductor longus muscles of rats flown approximately two weeks aboard the Cosmos 1887 and 2044 biosatellite flights. These lesions, characterized by breakage and loss of myofilaments and Z-line streaming, resembled damage induced by unaccustomed exercise that includes eccentric contractions in which muscles lengthen as they develop tension. We hypothesized that sarcomere lesions in atrophied muscles of space flow rats were not produced in microgravity by muscle unloading but resulted from muscle reloading upon re-exposure to terrestrial gravity. To test this hypothesis, we examined temporal changes in sarcomere integrity of adductor longus muscles from rats subjected to 12.5 days of hindlimb suspension unloading and subsequent reloading by return to vivarium cages for 0, 6, 12, or 48 hours of normal weightbearing. Our ultrastructural observations suggested that muscle unloading (0 h reloading) induced myofibril misalignment associated with myofiber atrophy. Muscle reloading for 6 hours induced focal sarcomere lesions in which cross striations were abnormally widened. Such lesions were electron lucent due to extensive myofilament loss. Lesions in reloaded muscles showed rapid restructuring. By 12 hours of reloading, lesions were moderately stained foci and by 48 hours darkly stained foci in which the pattern of cross striations was indistinct at the light and electron microscopic levels. These lesions were spanned by Z-line-like electron dense filamentous material. Our findings suggest a new role for Z-line streaming in lesion restructuring: rather than an antecedent to damage, this type of Z-line streaming may be indicative of rapid, early sarcomere repair.

  7. Histopathological changes in liver, kidney and muscles of pesticides exposed malnourished and diabetic rats.

    PubMed

    Benjamin, Nidhi; Kushwah, Ameeta; Sharma, R K; Katiyar, A K

    2006-03-01

    Histopathological changes were observed in liver, kidney and muscles of normal, protein-malnourished, diabetic as well as both protein-malnourished and diabetic albino rats when exposed to a mixture of monocrotophos, hexachlorocyclohexane and endosulfan at varying intervals. The examination revealed hepatotoxic, nephrotoxic and muscular necrotic effects in pesticides exposed rats. Toxicity was aggravated in protein-malnourished and diabetic animals and more so, if the animals were both diabetic and protein-malnourished.

  8. The Effect of Exercise Training on Skeletal Muscle Glucose Transorter Isoform GLUT4 Concentration in the Obese Zucker Rat

    DTIC Science & Technology

    1991-05-01

    NUMBERS The Effect of Exercise Training on Skeletal Muscle Glucose Transorter Isoform GLUT4 Concentration in the Obese Zucker Rat 6. AUTHOR(S) Eric A...Zr) THE EFFECT OF EXERCISE TRAINING ON SKELETAL MUSCLE GLUCOSE TRANSPORTER ISOFORM GLUT4 CONCENTRATION IN THE OBESE ZUCKER RAT by Eric Anthony Banks...laboratory for their help. Eric A. Banks v ABSTRACT THE EFFECT OF EXERCISE TRAINING ON SKELETAL MUSCLE GLUCOSE TRANSPORTER ISOFORM GLUT4 CONCENTRATION IN

  9. Effects of 8 wk of voluntary unloaded wheel running on K+ tolerance and excitability of soleus muscles in rat.

    PubMed

    Broch-Lips, Martin; de Paoli, Frank; Pedersen, Thomas Holm; Overgaard, Kristian; Nielsen, Ole Bækgaard

    2011-07-01

    During intense exercise, efflux of K(+) from working muscles increases extracellular K(+) ([K(+)](o)) to levels that can compromise muscle excitability and hence cause fatigue. In this context, the reduction in the exercise-induced elevation of [K(+)](o) observed after training in humans is suggested to contribute to the increased performance after training. Although a similar effect could be obtained by an increase in the tolerance of muscle to elevated [K(+)](o), this possibility has not been investigated. To examine this, isolated soleus muscles from sedentary (sedentary) rats and from rats that had voluntarily covered 13.1 ± 0.7 km/day in an unloaded running wheel for 8 wk (active) were compared. In muscles from active rats, the loss of force induced by exposure to an elevated [K(+)](o) of 9 mM was 42% lower than in muscles from sedentary rats (P < 0.001). This apparent increase in K(+) tolerance in active rats was associated with an increased excitability as evident from a 33% reduction in the electrical current needed to excite individual muscle fibers (P < 0.0009). Moreover, muscles from active rats had lower Cl(-) conductance, higher maximal rate of rise of single-fiber action potentials (AP), and higher Na(+)/K(+) pump content. When stimulated intermittently at 6.5 mM K(+), muscles from active rats displayed better endurance than muscles from sedentary rats, whereas no difference was found when the muscles were stimulated continuously at 30 or 120 Hz. We conclude that voluntary running increases muscle excitability, leading to improved tolerance to elevated [K(+)](o).

  10. Changes in glucose 1,6-bisphosphate content in rat skeletal muscle during contraction.

    PubMed Central

    Bassols, A M; Carreras, J; Cussó, R

    1986-01-01

    Glucose 1,6-bisphosphate, fructose 2,6-bisphosphate, glycogen, lactate and other glycolytic metabolites were measured in rat gastrocnemius muscle, which was electrically stimulated in situ via the sciatic nerve. Both the frequency and the duration of stimulation were varied to obtain different rates of glycolysis. There was no apparent relationship between fructose 2,6-bisphosphate content and lactate accumulation in contracting muscle. In contrast, glucose 1,6-bisphosphate content increased with lactate concentration during contraction. It is suggested that the increase in glucose 1,6-bisphosphate could play a role in phosphofructokinase stimulation and in the activation of the glycolytic flux during muscle contraction. PMID:3827864

  11. Effects of stretching and disuse on amino acids in muscles of rat hind limbs

    NASA Technical Reports Server (NTRS)

    Jaspers, Stephen R.; Henriksen, Erik J.; Satarug, Soisungwan; Tischler, Marc E.

    1989-01-01

    The effects of disuse and passive stretch on the concentrations of amino acids and ammonia in the unloaded soleus muscle was investigated in hindquarter-suspended (for six days by casting one foot in dorsiflexion) tail-casted rats. For a comparison with the condition of unloading, amino acids and ammonia were also measured in shortened extensor digitorum longus in the same casted limb and in denervated leg muscles. The results obtained suggest that passive stretch diminishes some of the characteristic alterations of amino acid concentrations due to unloading. This effect of stretch is considered to be due to the maintenance of muscle tension.

  12. [Effect of thyroidectomy on energetics of isometric muscle contraction in white rats].

    PubMed

    Soboliev, V I; Moskalets', T V

    2007-01-01

    The effect of thyroidactomia on parameters of energetics of isometric contractions of front shin--bone muscle of white rats is studied in in situ experiments. It is shown that experimental atiriosis lengthen considerably the latent period of muscle contractions (+95%) considerably reduce (in 5.5 times) the speed of it contraction in first phase of contraction act and also considerably increase the time (+37%), which necessery for developing maximum strength of contraction. Thyroidactomia with general negative influence on ergothropic characteristics of isometric muscle contraction decrease considerably the expenditure of thermal energy on maximum strength of contraction unit (-17%) or on middle isometric tension unit (-9.3%).

  13. Quantifying skeletal muscle recovery in a rat injury model using ultrasound imaging.

    PubMed

    Leineweber, Matt; Gao, Yingxin; Stouffer, James R

    2015-01-21

    Monitoring skeletal muscle health during recovery or degeneration is of great interest both clinically and in research settings. This type of monitoring requires health measurements be taken at multiple time points. Contraction strength is a commonly used metric for quantifying muscle health, but it requires invasive in vitro or in situ procedures that may further damage the tissue. Ultrasound imaging can be used to visualize muscle damage, and semi-quantitative grading scales have been shown to be effective at characterizing abnormalities. Using an established functional testing procedure in a rat model as a baseline measurement of muscle strength, we show that ultrasound imaging combined with a semi-quantitative grading scale can be used to monitor recovery after contusion injury. Although additional work is needed to refine the imaging and grading procedures, ultrasound promises a fast and non-invasive alternative to functional testing for characterizing skeletal muscle health.

  14. Effect of inactivity and passive stretch on protein turnover in phasic and postural rat muscles

    NASA Technical Reports Server (NTRS)

    Loughna, P.; Goldspink, G.; Goldspink, D. F.

    1986-01-01

    Muscle atrophy in humans can occur during prolonged bed rest, plaster cast immobilization, and space flight. In the present study, the suspension model used by Musacchia et al. (1983) is employed to investigate changes in protein synthesis and degradation in fast-twitch phasic (extensor digitorum longus) and slow-twitch postural (soleus) muscles in the rat, following hypokinesia and hypodynamia. In addition, the use of passive stretch was examined as a means of preventing atrophy. The obtained results suggest that the mechanisms controlling the processes of protein synthesis and protein breakdown during muscle disuse atrophy may be independent of each other. It appears, however, that the muscle atrophy due to hypokinesia and hypodynamia can be temporarily prevented by passively stretching a muscle.

  15. Proteomic and bioinformatic analyses of spinal cord injury-induced skeletal muscle atrophy in rats

    PubMed Central

    WEI, ZHI-JIAN; ZHOU, XIAN-HU; FAN, BAO-YOU; LIN, WEI; REN, YI-MING; FENG, SHI-QING

    2016-01-01

    Spinal cord injury (SCI) may result in skeletal muscle atrophy. Identifying diagnostic biomarkers and effective targets for treatment is an important challenge in clinical work. The aim of the present study is to elucidate potential biomarkers and therapeutic targets for SCI-induced muscle atrophy (SIMA) using proteomic and bioinformatic analyses. The protein samples from rat soleus muscle were collected at different time points following SCI injury and separated by two-dimensional gel electrophoresis and compared with the sham group. The identities of these protein spots were analyzed by mass spectrometry (MS). MS demonstrated that 20 proteins associated with muscle atrophy were differentially expressed. Bioinformatic analyses indicated that SIMA changed the expression of proteins associated with cellular, developmental, immune system and metabolic processes, biological adhesion and localization. The results of the present study may be beneficial in understanding the molecular mechanisms of SIMA and elucidating potential biomarkers and targets for the treatment of muscle atrophy. PMID:27177391

  16. De novo synthesis of purine nucleotides in different fiber types of rat skeletal muscle

    SciTech Connect

    Tullson, P.C.; John-Alder, H.; Hood, D.A.; Terjung, R.L.

    1986-03-01

    The contribution of de novo purine nucleotide synthesis to nucleotide metabolism in skeletal muscles is not known. The authors have determined rates of de novo synthesis in soleus (slow-twitch red), red gastrocnemius (fast-twitch red), and white gastrocnemius (fast-twitch white) using the perfused rat hindquarter. /sup 14/C glycine incorporation into ATP was linear after 1 and 2 hours of perfusion with 0.2 mM added glycine. The intracellular (I) and extracellular (E) specific activity of /sup 14/C glycine was determined by HPLC of phenylisothiocyanate derivatives of neutralized PCA extracts. The rates of de novo synthesis when expressed relative to muscle ATP content show slow and fast-twitch red muscles to be similar and about twice as great as fast-twitch white muscles. This could represent a greater turnover of the adenine nucleotide pool in more oxidative red muscle types.

  17. Hypogravity-induced atrophy of rat soleus and extensor digitorum longus muscles

    NASA Technical Reports Server (NTRS)

    Riley, D. A.; Ellis, S.; Slocum, G. R.; Satyanarayana, T.; Bain, J. L.; Sedlak, F. R.

    1987-01-01

    Prolonged exposure of humans to hypogravity causes weakening of their skeletal muscles. This problem was studied in rats exposed to hypogravity for 7 days aboard Spacelab 3. Hindlimb muscles were harvested 12-16 hours postflight for histochemical, biochemical, and ultrastructural analyses. The majority of the soleus and extensor digitorum longus fibers exhibited simple cell shrinkage. However, approximately 1% of the fibers in flight soleus muscles appeared necrotic. Flight muscle fibers showed increased glycogen, lower subsarcolemmal staining for mitochondrial enzymes, and fewer subsarcolemmal mitochondria. During atrophy, myofibrils were eroded by multiple focal losses of myofilaments; lysosomal autophagy was not evident. Tripeptidylaminopeptidase and calcium-activated protease activities of flight soleus fibers were significantly increased, implying a role in myofibril breakdown. Simple fiber atrophy appears to account for muscle weakening during spaceflight, but fiber necrosis is also a contributing factor.

  18. Somatotopy of the neurons innervating the cricothyroid, posterior cricoarytenoid, and thyroarytenoid muscles of the rat's larynx.

    PubMed

    Hernández-Morato, Ignacio; Pascual-Font, Arán; Ramírez, Carlos; Matarranz-Echeverría, Jorge; McHanwell, Stephen; Vázquez, Teresa; Sañudo, Jose R; Valderrama-Canales, Francisco J

    2013-03-01

    Neurons innervating the intrinsic muscles of the larynx are located within the nucleus ambiguus but the precise distribution of the neurons for each muscle is still a matter for debate. The purpose of this study was to finely determine the position and the number of the neurons innervating the intrinsic laryngeal muscles cricothyroid, posterior cricoarytenoid, and thyroarytenoid in the rat. The study was carried out in a total of 28 Sprague Dawley rats. The B subunit of the cholera toxin was employed as a retrograde tracer to determine the locations, within the nucleus ambiguus, of the neurons of these intrinsic laryngeal muscles following intramuscular injection. The labelled neurons were found ipsilaterally in the nucleus ambiguus grouped in discrete populations with reproducible rostrocaudal and dorsoventral locations among the sample of animals. Neurons innervating the cricothyroid muscle were located the most rostral of the three populations, neurons innervating the posterior cricoarytenoid were found more caudal, though there was a region of rostrocaudal overlap between these two populations. The most caudal were the neurons innervating the thyroarytenoid muscle, presenting a variable degree of overlap with the posterior cricoarytenoid muscle. The mean number (±SD) of labelled neurons was found to be 41 ± 9 for the cricothyroid, 39 ± 10 for the posterior cricoarytenoid and 33 ± 12 for the thyroarytenoid.

  19. Exercise training, glucose transporters, and glucose transport in rat skeletal muscles

    NASA Technical Reports Server (NTRS)

    Rodnick, K. J.; Henriksen, E. J.; James, D. E.; Holloszy, J. O.

    1992-01-01

    It was previously found that voluntary wheel running induces an increase in the insulin-sensitive glucose transporter, i.e., the GLUT4 isoform, in rat plantaris muscle (K. J. Rodnick, J. O. Holloszy, C. E. Mondon, and D. E. James. Diabetes 39: 1425-1429, 1990). The present study was undertaken to determine whether 1) the increase in muscle GLUT4 protein is associated with an increase in maximally stimulated glucose transport activity, 2) a conversion of type IIb to type IIa or type I muscle fibers plays a role in the increase in GLUT4 protein, and 3) an increase in the GLUT1 isoform is a component of the adaptation of muscle to endurance exercise. Five weeks of voluntary wheel running that resulted in a 33% increase in citrate synthase activity induced a 50% increase in GLUT4 protein in epitrochlearis muscles of female Sprague-Dawley rats. The rate of 2-deoxy-glucose transport maximally stimulated with insulin or insulin plus contractions was increased approximately 40% (P less than 0.05). There was no change in muscle fiber type composition, evaluated by myosin ATPase staining, in the epitrochlearis. There was also no change in GLUT1 protein concentration. We conclude that an increase in GLUT4, but not of GLUT1 protein, is a component of the adaptive response of muscle to endurance exercise and that the increase in GLUT4 protein is associated with an increased capacity for glucose transport.

  20. A novel insulin sensitizer (S15511) enhances insulin-stimulated glucose uptake in rat skeletal muscles.

    PubMed

    Jessen, N; Selmer Buhl, E; Pold, R; Schmitz, O; Lund, S

    2008-04-01

    Type 2 diabetes is preceded by the presence of skeletal muscle insulin resistance, and drugs that increase insulin sensitivity in skeletal muscle prevent the disease. S15511 is an original compound with demonstrated effects on insulin sensitivity in animal models of insulin resistance. However, the mechanisms behind the insulin-sensitizing effect of S15511 are unknown. The aim of our study was to explore whether S15511 improves insulin sensitivity in skeletal muscles. Insulin sensitivity was assessed in skeletal muscles from S15511-treated rats by measuring intracellular insulin-signaling activity and insulin-stimulated glucose transport in isolated muscles. In addition, GLUT4 expression and glycogen levels were assessed after treatment. S15511 treatment was associated with an increase in insulin-stimulated glucose transport in type IIb fibers, while type I fibers were unaffected. The enhanced glucose transport was mirrored by a fiber type-specific increase in GLUT4 expression, while no improvement in insulin-signaling activity was observed. S15511 is a novel insulin sensitizer that is capable of improving glucose homeostasis in nondiabetic rats. The compound enhances skeletal muscle insulin sensitivity and specifically targets type IIb muscle fibers by increasing GLUT4 expression. Together these data show S15511 to be a potentially promising new drug in the treatment and prevention of type 2 diabetes.

  1. A method to test contractility of the supraspinatus muscle in mouse, rat, and rabbit

    PubMed Central

    Valencia, Ana P.; Iyer, Shama R.; Pratt, Stephen J. P.; Gilotra, Mohit N.

    2015-01-01

    The rotator cuff (RTC) muscles not only generate movement but also provide important shoulder joint stability. RTC tears, particularly in the supraspinatus muscle, are a common clinical problem. Despite some biological healing after RTC repair, persistent problems include poor functional outcomes with high retear rates after surgical repair. Animal models allow further exploration of the sequela of RTC injury such as fibrosis, inflammation, and fatty infiltration, but there are few options regarding contractility for mouse, rat, and rabbit. Histological findings can provide a “direct measure” of damage, but the most comprehensive measure of the overall health of the muscle is contractile force. However, information regarding normal supraspinatus size and contractile function is scarce. Animal models provide the means to compare muscle histology, imaging, and contractility within individual muscles in various models of injury and disease, but to date, most testing of animal contractile force has been limited primarily to hindlimb muscles. Here, we describe an in vivo method to assess contractility of the supraspinatus muscle and describe differences in methods and representative outcomes for mouse, rat, and rabbit. PMID:26586911

  2. The Impact of Muscle Disuse on Muscle Atrophy in Severely Burned Rats

    DTIC Science & Technology

    2010-12-01

    Herrick RE, Baldwin KM. Effect of anabolic steroids on skeletal muscle mass during hindlimb suspension. J Appl Physiol 1987;63(5):2122–2127. [PubMed...physical activity also shows advantages in enhancing and improving recovery from muscle catabolism after severe burn [49]. Similarly, both anabolic

  3. Statin or fibrate chronic treatment modifies the proteomic profile of rat skeletal muscle.

    PubMed

    Camerino, Giulia Maria; Pellegrino, Maria Antonietta; Brocca, Lorenza; Digennaro, Claudio; Camerino, Diana Conte; Pierno, Sabata; Bottinelli, Roberto

    2011-04-15

    Statins and fibrates can cause myopathy. To further understand the causes of the damage we performed a proteome analysis in fast-twitch skeletal muscle of rats chronically treated with different hypolipidemic drugs. The proteomic maps were obtained from extensor digitorum longus (EDL) muscles of rats treated for 2-months with 10mg/kg atorvastatin, 20 mg/kg fluvastatin, 60 mg/kg fenofibrate and control rats. The proteins differentially expressed were identified by mass spectrometry and further analyzed by immunoblot analysis. We found a significant modification in 40 out of 417 total spots analyzed in atorvastatin treated rats, 15 out of 436 total spots in fluvastatin treated rats and 21 out of 439 total spots in fenofibrate treated rats in comparison to controls. All treatments induced a general tendency to a down-regulation of protein expression; in particular, atorvastatin affected the protein pattern more extensively with respect to the other treatments. Energy production systems, both oxidative and glycolytic enzymes and creatine kinase, were down-regulated following atorvastatin administration, whereas fenofibrate determined mostly alterations in glycolytic enzymes and creatine kinase, oxidative enzymes being relatively spared. Additionally, all treatments resulted in some modifications of proteins involved in cellular defenses against oxidative stress, such as heat shock proteins, and of myofibrillar proteins. These results were confirmed by immunoblot analysis. In conclusions, the proteomic analysis showed that either statin or fibrate administration can modify the expression of proteins essential for skeletal muscle function suggesting potential mechanisms for statin myopathy.

  4. Expression Profile of Nerve Growth Factor after Muscle Incision in the Rat

    PubMed Central

    Wu, Chaoran; Erickson, Mark A.; Xu, Jun; Wild, Kenneth D.; Brennan, Timothy J.

    2009-01-01

    Background Previous studies have demonstrated that nerve growth factor (NGF) is an important mediator of pathologic pain. Many studies have focused on cutaneous mechanisms for NGF-induced hyperalgesia; few have examined its contribution in deeper tissues like muscle. This study examined pain behaviors and the expression of NGF in incised hind paw flexor digitorum brevis muscle. Methods Adult Sprague-Dawley rats were pretreated with anti-NGF peptibody and underwent skin or skin plus deep fascia and muscle incision. Guarding pain behaviors were measured. Muscle NGF messenger RNA (mRNA) was measured by real time polymerase chain reaction. Changes in NGF protein expression were measured using western blot, enzyme-linked immunoabsorbent assay and immunohistochemistry. In situ hybridization for NGF mRNA was also performed. Results Pretreatment with anti-NGF peptibody (100 mg/kg) decreased the guarding behavior caused by deep fascia and muscle incision. Muscle NGF mRNA increased abruptly 2 h after incision and was the same as control by postoperative day 1. NGF protein increased from 4 h after incision, and was sustained for several days. NGF was localized in many calcitonin gene related peptide positive axons, few N52 positive axons, but not isolectin B4 positive axons in incised muscle. The sources of NGF mRNA included keratinocytes in epidermis and fibroblasts in deeper tissues. Conclusion Fibroblasts adjacent to the injury are sources of NGF in incised muscle. NGF is upregulated by incision of muscle and contributes to guarding pain behavior. PMID:19104181

  5. Mild Hyperbaric Oxygen Improves Decreased Oxidative Capacity of Spinal Motoneurons Innervating the Soleus Muscle of Rats with Type 2 Diabetes.

    PubMed

    Takemura, Ai; Ishihara, Akihiko

    2016-09-01

    Rats with type 2 diabetes exhibit decreased oxidative capacity, such as reduced oxidative enzyme activity, low-intensity staining for oxidative enzymes in fibers, and no high-oxidative type IIA fibers, in the skeletal muscle, especially in the soleus muscle. In contrast, there are no data available concerning the oxidative capacity of spinal motoneurons innervating skeletal muscle of rats with type 2 diabetes. This study examined the oxidative capacity of motoneurons innervating the soleus muscle of non-obese rats with type 2 diabetes. In addition, this study examined the effects of mild hyperbaric oxygen at 1.25 atmospheres absolute with 36 % oxygen for 10 weeks on the oxidative capacity of motoneurons innervating the soleus muscle because mild hyperbaric oxygen improves the decreased oxidative capacity of the soleus muscle in non-obese rats with type 2 diabetes. Spinal motoneurons innervating the soleus muscle were identified using nuclear yellow, a retrograde fluorescent neuronal tracer. Thereafter, the cell body sizes and succinate dehydrogenase activity of identified motoneurons were analyzed. Decreased succinate dehydrogenase activity of small-sized alpha motoneurons innervating the soleus muscle was observed in rats with type 2 diabetes. The decreased succinate dehydrogenase activity of these motoneurons was improved by mild hyperbaric oxygen. Therefore, we concluded that rats with type 2 diabetes have decreased oxidative capacity in motoneurons innervating the soleus muscle and this decreased oxidative capacity is improved by mild hyperbaric oxygen.

  6. Fenofibrate administration to arthritic rats increases adiponectin and leptin and prevents oxidative muscle wasting

    PubMed Central

    Castillero, Estíbaliz; Martín, Ana Isabel; Nieto-Bona, Maria Paz; Fernández-Galaz, Carmen; López-Menduiña, María; Villanúa, María Ángeles; López-Calderón, Asunción

    2012-01-01

    Chronic inflammation induces skeletal muscle wasting and cachexia. In arthritic rats, fenofibrate, a peroxisome proliferator-activated receptor α (PPARα (PPARA)) agonist, reduces wasting of gastrocnemius, a predominantly glycolytic muscle, by decreasing atrogenes and myostatin. Considering that fenofibrate increases fatty acid oxidation, the aim of this study was to elucidate whether fenofibrate is able to prevent the effect of arthritis on serum adipokines and on soleus, a type I muscle in which oxidative metabolism is the dominant source of energy. Arthritis was induced by injection of Freund's adjuvant. Four days after the injection, control and arthritic rats were gavaged daily with fenofibrate (300 mg/kg bw) or vehicle over 12 days. Arthritis decreased serum leptin, adiponectin, and insulin (P<0.01) but not resistin levels. In arthritic rats, fenofibrate administration increased serum concentrations of leptin and adiponectin. Arthritis decreased soleus weight, cross-sectional area, fiber size, and its Ppar α mRNA expression. In arthritic rats, fenofibrate increased soleus weight, fiber size, and Ppar α expression and prevented the increase in Murf1 mRNA. Fenofibrate decreased myostatin, whereas it increased MyoD (Myod1) and myogenin expressions in the soleus of control and arthritic rats. These data suggest that in oxidative muscle, fenofibrate treatment is able to prevent arthritis-induced muscle wasting by decreasing Murf1 and myostatin expression and also by increasing the myogenic regulatory factors, MyoD and myogenin. Taking into account the beneficial action of adiponectin on muscle wasting and the correlation between adiponectin and soleus mass, part of the anticachectic action of fenofibrate may be mediated through stimulation of adiponectin secretion. PMID:23781298

  7. Systemic response to thermal injury in rats. Accelerated protein degradation and altered glucose utilization in muscle.

    PubMed Central

    Clark, A S; Kelly, R A; Mitch, W E

    1984-01-01

    Negative nitrogen balance and increased oxygen consumption after thermal injury in humans and experimental animals is related to the extent of the burn. To determine whether defective muscle metabolism is restricted to the region of injury, we studied protein and glucose metabolism in forelimb muscles of rats 48 h after a scalding injury of their hindquarters. This injury increased muscle protein degradation (PD) from 140 +/- 5 to 225 +/- 5 nmol tyrosine/g per h, but did not alter protein synthesis. Muscle lactate release was increased greater than 70%, even though plasma catecholamines and muscle cyclic AMP were not increased. Insulin dose-response studies revealed that the burn decreased the responsiveness of muscle glycogen synthesis to insulin but did not alter its sensitivity to insulin. Rates of net glycolysis and glucose oxidation were increased and substrate cycling of fructose-6-phosphate was decreased at all levels of insulin. The burn-induced increase in protein and glucose catabolism was not mediated by adrenal hormones, since they persisted despite adrenalectomy. Muscle PGE2 production was not increased by the burn and inhibition of prostaglandin synthesis by indomethacin did not inhibit proteolysis. The increase in PD required lysosomal proteolysis, since inhibition of cathepsin B with EP475 reduced PD. Insulin reduced PD 20% and the effects of EP475 and insulin were additive, reducing PD 41%. An inhibitor of muscle PD, alpha-ketoisocaproate, reduced burn-induced proteolysis 28% and lactate release 56%. The rate of PD in muscle of burned and unburned rats was correlated with the percentage of glucose uptake that was directed into lactate production (r = +0.82, P less than 0.01). Thus, a major thermal injury causes hypercatabolism of protein and glucose in muscle that is distant from the injury, and these responses may be linked to a single metabolic defect. PMID:6470144

  8. Relationship between membrane Cl− conductance and contractile endurance in isolated rat muscles

    PubMed Central

    de Paoli, Frank Vincenzo; Broch-Lips, Martin; Pedersen, Thomas Holm; Nielsen, Ole Bækgaard

    2013-01-01

    Resting skeletal muscle fibres have a large membrane Cl− conductance (GCl) that dampens their excitability. Recently, however, muscle activity was shown to induce PKC-mediated reduction in GCl in rat muscles of 40–90%. To examine the physiological significance of this PKC-mediated GCl reduction for the function of muscles, this study explored effects of GCl reductions on contractile endurance in isolated rat muscles. Contractile endurance was assessed from the ability of muscle to maintain force during prolonged stimulation under conditions when GCl was manipulated by: (i) inhibition of PKC, (ii) reduction of solution Cl− or (iii) inhibition of ClC-1 Cl− channels using 9-anthracene-carboxylic acid (9-AC). Experiments showed that contractile endurance was optimally preserved by reductions in GCl similar to what occurs in active muscle. Contrastingly, further GCl reductions compromised the endurance. The experiments thus show a biphasic relationship between GCl and contractile endurance in which partial GCl reduction improves endurance while further GCl reduction compromises endurance. Intracellular recordings of trains of action potentials suggest that this biphasic dependency of contractile endurance on GCl reflects that lowering GCl enhances muscle excitability but low GCl also increases the depolarisation of muscle fibres during excitation and reduces their ability to re-accumulate K+ lost during excitation. If GCl becomes very low, the latter actions dominate causing reduced endurance. It is concluded that the PKC-mediated ClC-1 channel inhibition in active muscle reduces GCl to a level that optimises contractile endurance during intense exercise. PMID:23045345

  9. Exercise training increases protein O-GlcNAcylation in rat skeletal muscle.

    PubMed

    Hortemo, Kristin Halvorsen; Lunde, Per Kristian; Anonsen, Jan Haug; Kvaløy, Heidi; Munkvik, Morten; Rehn, Tommy Aune; Sjaastad, Ivar; Lunde, Ida Gjervold; Aronsen, Jan Magnus; Sejersted, Ole M

    2016-09-01

    Protein O-GlcNAcylation has emerged as an important intracellular signaling system with both physiological and pathophysiological functions, but the role of protein O-GlcNAcylation in skeletal muscle remains elusive. In this study, we tested the hypothesis that protein O-GlcNAcylation is a dynamic signaling system in skeletal muscle in exercise and disease. Immunoblotting showed different protein O-GlcNAcylation pattern in the prototypical slow twitch soleus muscle compared to fast twitch EDL from rats, with greater O-GlcNAcylation level in soleus associated with higher expression of the modulating enzymes O-GlcNAc transferase (OGT), O-GlcNAcase (OGA), and glutamine fructose-6-phosphate amidotransferase isoforms 1 and 2 (GFAT1, GFAT2). Six weeks of exercise training by treadmill running, but not an acute exercise bout, increased protein O-GlcNAcylation in rat soleus and EDL There was a striking increase in O-GlcNAcylation of cytoplasmic proteins ~50 kDa in size that judged from mass spectrometry analysis could represent O-GlcNAcylation of one or more key metabolic enzymes. This suggests that cytoplasmic O-GlcNAc signaling is part of the training response. In contrast to exercise training, postinfarction heart failure (HF) in rats and humans did not affect skeletal muscle O-GlcNAcylation level, indicating that aberrant O-GlcNAcylation cannot explain the skeletal muscle dysfunction in HF Human skeletal muscle displayed extensive protein O-GlcNAcylation that by large mirrored the fiber-type-related O-GlcNAcylation pattern in rats, suggesting O-GlcNAcylation as an important signaling system also in human skeletal muscle.

  10. Comparison of soleus muscles from rats exposed to microgravity for 10 versus 14 days

    NASA Technical Reports Server (NTRS)

    Staron, R. S.; Kraemer, W. J.; Hikida, R. S.; Reed, D. W.; Murray, J. D.; Campos, G. E.; Gordon, S. E.

    1998-01-01

    The effects of two different duration space-flights on the extent of atrophy, fiber type composition, and myosin heavy chain (MHC) content of rat soleus muscles were compared. Adult male Fisher rats (n=12) were aboard flight STS-57 and exposed to 10 days of microgravity and adult ovariectomized female Spraque-Dawley rats (n=12) were aboard flight STS-62 for 14 days. Soleus muscles were bilaterally removed from the flight and control animals and frozen for subsequent analyses. Muscle wet weights, fiber types (I, IC, IIC, and IIA), cross-sectional area, and MHC content were determined. Although a significant difference was found between the soleus wet weights of the two ground-based control groups, they were similar with regard to MHC content (ca 90% MHCI and ca 10% MHCIIa) and fiber type composition. Unloading of the muscles caused slow-to-fast transformations which included a decrease in the percentage of type I fibers and MHCI, an increase in fibers classified as type IC, and the expression of two fast myosin heavy chains not found in the control rat soleus muscles (MHCIId and MHCIIb). Although the amount of atrophy (ca 26%) and the extent of slow-to-fast transformation (decrease in the percentage of MHCI from 90% to 82.5%) in the soleus muscles were similar between the two spaceflights, the percentages of the fast MHCs differed. After 14 days of spaceflight, the percentage of MHCIIa was significantly lower and the percentages of MHCIId and MHCIIb were significantly higher than the corresponding MHC content of the soleus muscles from the 10-day animals. Indeed, MHCIId became the predominant fast MHC after 14 days in space. These data suggest fast-to-faster transformations continued during the longer spaceflight.

  11. Metabolomic profiling reveals severe skeletal muscle group-specific perturbations of metabolism in aged FBN rats.

    PubMed

    Garvey, Sean M; Dugle, Janis E; Kennedy, Adam D; McDunn, Jonathan E; Kline, William; Guo, Lining; Guttridge, Denis C; Pereira, Suzette L; Edens, Neile K

    2014-06-01

    Mammalian skeletal muscles exhibit age-related adaptive and pathological remodeling. Several muscles in particular undergo progressive atrophy and degeneration beyond median lifespan. To better understand myocellular responses to aging, we used semi-quantitative global metabolomic profiling to characterize trends in metabolic changes between 15-month-old adult and 32-month-old aged Fischer 344 × Brown Norway (FBN) male rats. The FBN rat gastrocnemius muscle exhibits age-dependent atrophy, whereas the soleus muscle, up until 32 months, exhibits markedly fewer signs of atrophy. Both gastrocnemius and soleus muscles were analyzed, as well as plasma and urine. Compared to adult gastrocnemius, aged gastrocnemius showed evidence of reduced glycolytic metabolism, including accumulation of glycolytic, glycogenolytic, and pentose phosphate pathway intermediates. Pyruvate was elevated with age, yet levels of citrate and nicotinamide adenine dinucleotide were reduced, consistent with mitochondrial abnormalities. Indicative of muscle atrophy, 3-methylhistidine and free amino acids were elevated in aged gastrocnemius. The monounsaturated fatty acids oleate, cis-vaccenate, and palmitoleate also increased in aged gastrocnemius, suggesting altered lipid metabolism. Compared to gastrocnemius, aged soleus exhibited far fewer changes in carbohydrate metabolism, but did show reductions in several glycolytic intermediates, fumarate, malate, and flavin adenine dinucleotide. Plasma biochemicals showing the largest age-related increases included glycocholate, heme, 1,5-anhydroglucitol, 1-palmitoleoyl-glycerophosphocholine, palmitoleate, and creatine. These changes suggest reduced insulin sensitivity in aged FBN rats. Altogether, these data highlight skeletal muscle group-specific perturbations of glucose and lipid metabolism consistent with mitochondrial dysfunction in aged FBN rats.

  12. Aging affects passive stiffness and spindle function of the rat soleus muscle.

    PubMed

    Rosant, Cédric; Nagel, Marie-Danielle; Pérot, Chantal

    2007-04-01

    Aging affects many motor functions, notably the spinal stretch reflexes and muscle spindle sensitivity. Spindle activation also depends on the elastic properties of the structures linked to the proprioceptive receptors. We have calculated a spindle efficacy index, SEI, for old rats. This index relates the spindle sensitivity, deduced from electroneurograms recording (ENG), to the passive stiffness of the muscle. Spindle sensitivity and passive incremental stiffness were calculated during ramp and hold stretches imposed on pseudo-isolated soleus muscles of control rats (aged 4 months, n=12) and old rats (aged 24 months, n=16). SEI were calculated for the dynamic and static phases of ramp (1-80 mm/s) and for hold (0.5-2mm) stretches imposed at two reference lengths: length threshold for spindle afferents discharges, L(n) (neurogram length) and slack length, L(s). The passive incremental stiffness was calculated from the peak and steady values of passive tension, measured under the stretch conditions used for the ENG recordings, and taking into account the muscle cross-sectional area. The pseudo-isolated soleus muscles were also stretched to establish the stress-strain relationship and to calculate muscle stiffness constant. The contralateral muscle was used to count muscle spindles and spindle fibers (ATPase staining) and immunostained to identify MyHC isoforms. L(n) and L(s) lengths were not significantly different in the control group, while L(n) was significantly greater than L(s) in old muscles. Under dynamic conditions, the SEI of old muscles was the same as in controls at L(s), but it was significantly lower than in controls at L(n) due to increased passive incremental stiffness under the stretch conditions used to analyze the ENG. Under static conditions, the SEI of old muscles was significantly lower than control values at all the stretch amplitudes and threshold lengths tested, due to increased passive incremental stiffness and decreased spindle sensitivity

  13. Interactive effects of growth hormone and exercise on muscle mass in suspended rats

    NASA Technical Reports Server (NTRS)

    Grindeland, Richard E.; Roy, Roland R.; Edgerton, V. Reggie; Grossman, Elena J.; Mukku, Venkat R.; Jiang, Bian; Pierotti, David J.; Rudolph, Ingrid

    1994-01-01

    Measures to attenuate muscle atrophy in rats in response to simulated microgravity (hindlimb suspension (HS)) have been only partially successful. In the present study, hypophysectomized rats were in HS for 7 days, and the effects of recombinant human growth hormone (GH), exercise (Ex), or GH+Ex on the weights, protein concentrations, and fiber cross-sectional areas (CSAs) of hindlimb muscles were determined. The weights of four extensor muscles, i.e., the soleus (Sol), medial (MG) and lateral (LG) gastrocnemius, and plantaris (Plt), and one adductor, i.e., the adductor longus (AL), were decreased by 10-22% after HS. Fiber CSAs were decreased by 34% in the Sol and by 1 17% in the MG after HS. In contrast, two flexors, i.e., the tibialis anterior (TA) and extensor digitorum longus (EDL), did not atrophy. In HS rats, GH treatment alone maintained the weights of the fast extensors (MG, LG, Plt) and flexors (TA, EDL) at or above those of control rats. This effect was not observed in the slow extensor (Sol) or AL. Exercise had no significant effect on the weight of any muscle in HS rats. A combination of GH and Ex treatments yielded a significant increase in the weights of the fast extensors and in the CSA of both fast and slow fibers of the MG and significantly increased Sol weight and CSA of the slow fibers of the Sol. The AL was not responsive to either GH or Ex treatments. Protein concentrations of the Sol and MG were higher only in the Sol of Ex and GH+Ex rats. These results suggest that while GH treatment or intermittent high intensity exercise alone have a minimal effect in maintaining the mass of unloaded muscle, there is a strong interactive effect of these two treatments.

  14. Melatonin prevents mitochondrial dysfunction and insulin resistance in rat skeletal muscle.

    PubMed

    Teodoro, Bruno G; Baraldi, Flavia G; Sampaio, Igor H; Bomfim, Lucas H M; Queiroz, André L; Passos, Madla A; Carneiro, Everardo M; Alberici, Luciane C; Gomis, Ramon; Amaral, Fernanda G; Cipolla-Neto, José; Araújo, Michel B; Lima, Tanes; Akira Uyemura, Sérgio; Silveira, Leonardo R; Vieira, Elaine

    2014-09-01

    Melatonin has a number of beneficial metabolic actions and reduced levels of melatonin may contribute to type 2 diabetes. The present study investigated the metabolic pathways involved in the effects of melatonin on mitochondrial function and insulin resistance in rat skeletal muscle. The effect of melatonin was tested both in vitro in isolated rats skeletal muscle cells and in vivo using pinealectomized rats (PNX). Insulin resistance was induced in vitro by treating primary rat skeletal muscle cells with palmitic acid for 24 hr. Insulin-stimulated glucose uptake was reduced by palmitic acid followed by decreased phosphorylation of AKT which was prevented my melatonin. Palmitic acid reduced mitochondrial respiration, genes involved in mitochondrial biogenesis and the levels of tricarboxylic acid cycle intermediates whereas melatonin counteracted all these parameters in insulin-resistant cells. Melatonin treatment increases CAMKII and p-CREB but had no effect on p-AMPK. Silencing of CREB protein by siRNA reduced mitochondrial respiration mimicking the effect of palmitic acid and prevented melatonin-induced increase in p-AKT in palmitic acid-treated cells. PNX rats exhibited mild glucose intolerance, decreased energy expenditure and decreased p-AKT, mitochondrial respiration, and p-CREB and PGC-1 alpha levels in skeletal muscle which were restored by melatonin treatment in PNX rats. In summary, we showed that melatonin could prevent mitochondrial dysfunction and insulin resistance via activation of CREB-PGC-1 alpha pathway. Thus, the present work shows that melatonin play an important role in skeletal muscle mitochondrial function which could explain some of the beneficial effects of melatonin in insulin resistance states.

  15. Biochemical and histochemical adaptations of skeletal muscle to rat suspension

    NASA Technical Reports Server (NTRS)

    Templeton, G. H.

    1984-01-01

    The influence of rat suspension on soleus disuse and atrophy was investigated to measure changes in fiber area and number and to determine if suspension elicited changes in lysosomal protease activity and rate of calcium uptake by the sarcoplasmic reticulum. The infuence of rat suspension on myosin light chain phosphorylation and succinate dehydrogenase activity are determined.

  16. Skeletal Muscle Satellite Cell Activation Following Cutaneous Burn in Rats

    DTIC Science & Technology

    2013-12-01

    mechanisms of long-term muscle atrophy. # 2012 Elsevier Ltd and ISBI. All rights reserved. * Corresponding author at: US Army Institute of Surgical...understanding of the impact of burn on satellite cell functionality will allow us to identify the cellular mechanisms of long-term muscle atrophy after...fibers. J Biophys Biochem Cytol 1961;9:493–5. [12] Hawke TJ, Garry DJ. Myogenic satellite cells: physiology to molecular biology. J Appl Physiol 2001;91

  17. Smooth muscle adaptation and recovery of contractility after massive small bowel resection in rats.

    PubMed

    Chen, Jie; Wen, Jie; Cai, Wei

    2012-05-01

    Previous studies have suggested that massive small bowel resection (mSBR) compromises the normal intestinal processes of digestion and absorption, and requires an adaptive response to regain full function and reinstate coordinated contractile activity of the circular smooth muscle. This study was designed to investigate spontaneous contractile activity of circular smooth muscle using the mSBR rat model and to determine the functional role of M(2) and M(3) muscarinic acetylcholine receptors (mAChR) in this process. Male Sprague-Dawley rats underwent an 80% proximal SBR or sham operation. Markers of adaptation, including villus and microvillus height, were analyzed by hematoxylin and eosin staining and transmission electron microscopy. Contractility was measured by attaching the distal ileum strips to strain gauge transducers and exposing the tissue to varying doses of the cholinergic agonist carbachol. Protein expressions of M(2)- and M(3)-mAChR in intestinal smooth muscle (ISM) were detected by Western blot. Following mSBR, the ISM showed perturbed spontaneous rhythmic contraction, irregular amplitude and slow frequency by muscle strip test. However, by two weeks after mSBR, the contractile function of circular smooth muscle was found to have returned to normal levels. Protein expression of M(2)-mAChR was down-regulated following mSBR but up-regulated during the adaptive process when contractile activity of circular smooth muscle was regained. These results indicate that smooth muscle contractility was spontaneously restored in rats following mSBR, and involved the acetylcholine receptors M(2) and M(3). Thus, the disrupted contractile response of smooth muscle in short bowel syndrome may be corrected by therapeutic intervention to restore the expressions of M(2)- and M(3)-mAChR to pre-mSBR levels.

  18. Regional blood flow and skeletal muscle energy status in endotoxemic rats

    SciTech Connect

    Jepson, M.M.; Cox, M.; Bates, P.C.; Rothwell, N.J.; Stock, M.J.; Cady, E.B.; Millward, D.J.

    1987-05-01

    Endotoxins induce muscle wasting in part as a result of depressed protein synthesis. To investigate whether these changes reflect impaired energy transduction, blood flow, O/sub 2/ extraction, and high-energy phosphates in muscle and whole-body O/sub 2/ consumption (Vo/sub 2/) have been measured. Vo/sub 2/ was measured for 6 h after an initial sublethal dose of endotoxin (Escherichia coli lipopolysaccharide 0.3 mg/100 g body wt sc) or saline and during 6 h after a second dose 24 h later. In fed or fasted rats, Vo/sub 2/ was either increased or better maintained after endotoxin. In anesthetized fed rats 3-4 h after the second dose of endotoxin Vo/sub 2/ was increased, and this was accompanied by increased blood flow measured by /sup 57/Co-labelled microspheres to liver (hepatic arterial supply), kidney, and perirenal brown adipose tissue and a 57 and 64% decrease in flow to back and hindlimb muscle, respectively, with no change in any other organ. Hindlimb arteriovenous O/sub 2/ was unchanged, indicating markedly decreased aerobic metabolism in muscle, and the contribution of the hindlimb to whole-body Vo/sub 2/ decreased by 46%. Adenosine 5'-triphosphate levels in muscle were unchanged in endotoxin-treated rats, and this was confirmed by topical nuclear magnetic resonance spectroscopy, which also showed muscle pH to be unchanged. These results show that, although there is decreased blood flow and aerobic oxidation in muscle, adenosine 5'-triphosphate availability does not appear to be compromised so that the endotoxin-induced muscle catabolism and decreased protein synthesis must reflex some other mechanism.

  19. Metabolic acidosis stimulates protein degradation in rat muscle by a glucocorticoid-dependent mechanism.

    PubMed Central

    May, R C; Kelly, R A; Mitch, W E

    1986-01-01

    Metabolic acidosis is associated with enhanced renal ammonia-genesis which is regulated, in part, by glucocorticoids. The interaction between glucocorticoids and chronic metabolic acidosis on nitrogen utilization and muscle protein metabolism is unknown. In rats pair-fed by gavage, we found that chronic acidosis stunted growth and caused a 43% increase in urinary nitrogen and an 87% increase in urinary corticosterone. Net protein degradation in incubated epitrochlearis muscles from chronically acidotic rats was stimulated at all concentrations of insulin from 0 to 10(4) microU/ml. This effect of acidosis persisted despite supplementation of the media with amino acids with or without insulin, indomethacin, and inhibitors of lysosomal thiol cathepsins. Acidosis did not change protein synthesis; hence, the increase in net protein degradation was caused by stimulation of proteolysis. Acidosis did not increase glutamine production in muscle. The protein catabolic effect of acidosis required glucocorticoids; protein degradation was stimulated in muscle of acidotic, adrenalectomized rats only if they were treated with dexamethasone. Moreover, when nonacidotic animals were given 3 micrograms/100 g of body weight dexamethasone twice a day, muscle protein degradation was increased if the muscles were simply incubated in acidified media. We conclude that chronic metabolic acidosis depresses nitrogen utilization and increases glucocorticoid production. The combination of increased glucocorticoids and acidosis stimulates muscle proteolysis but does not affect protein synthesis. These changes in muscle protein metabolism may play a role in the defense against acidosis by providing amino acid nitrogen to support the glutamine production necessary for renal ammoniagenesis. PMID:3511100

  20. Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure

    NASA Technical Reports Server (NTRS)

    Delp, M. D.; Duan, C.; Mattson, J. P.; Musch, T. I.

    1997-01-01

    One of the primary consequences of left ventricular dysfunction (LVD) after myocardial infarction is a decrement in exercise capacity. Several factors have been hypothesized to account for this decrement, including alterations in skeletal muscle metabolism and aerobic capacity. The purpose of this study was to determine whether LVD-induced alterations in skeletal muscle enzyme activities, fiber composition, and fiber size are 1) generalized in muscles or specific to muscles composed primarily of a given fiber type and 2) related to the severity of the LVD. Female Wistar rats were divided into three groups: sham-operated controls (n = 13) and rats with moderate (n = 10) and severe (n = 7) LVD. LVD was surgically induced by ligating the left main coronary artery and resulted in elevations (P < 0.05) in left ventricular end-diastolic pressure (sham, 5 +/- 1 mmHg; moderate LVD, 11 +/- 1 mmHg; severe LVD, 25 +/- 1 mmHg). Moderate LVD decreased the activities of phosphofructokinase (PFK) and citrate synthase in one muscle composed of type IIB fibers but did not modify fiber composition or size of any muscle studied. However, severe LVD diminished the activity of enzymes involved in terminal and beta-oxidation in muscles composed primarily of type I fibers, type IIA fibers, and type IIB fibers. In addition, severe LVD induced a reduction in the activity of PFK in type IIB muscle, a 10% reduction in the percentage of type IID/X fibers, and a corresponding increase in the portion of type IIB fibers. Atrophy of type I fibers, type IIA fibers, and/or type IIB fibers occurred in soleus and plantaris muscles of rats with severe LVD. These data indicate that rats with severe LVD after myocardial infarction exhibit 1) decrements in mitochondrial enzyme activities independent of muscle fiber composition, 2) a reduction in PFK activity in type IIB muscle, 3) transformation of type IID/X to type IIB fibers, and 4) atrophy of type I, IIA, and IIB fibers.

  1. Localized infusion of IGF-I results in skeletal muscle hypertrophy in rats

    NASA Technical Reports Server (NTRS)

    Adams, G. R.; McCue, S. A.

    1998-01-01

    Insulin-like growth factor I (IGF-I) peptide levels have been shown to increase in overloaded skeletal muscles (G. R. Adams and F. Haddad. J. Appl. Physiol. 81: 2509-2516, 1996). In that study, the increase in IGF-I was found to precede measurable increases in muscle protein and was correlated with an increase in muscle DNA content. The present study was undertaken to test the hypothesis that direct IGF-I infusion would result in an increase in muscle DNA as well as in various measurements of muscle size. Either 0.9% saline or nonsystemic doses of IGF-I were infused directly into a non-weight-bearing muscle of rats, the tibialis anterior (TA), via a fenestrated catheter attached to a subcutaneous miniosmotic pump. Saline infusion had no effect on the mass, protein content, or DNA content of TA muscles. Local IGF-I infusion had no effect on body or heart weight. The absolute weight of the infused TA muscles was approximately 9% greater (P < 0.05) than that of the contralateral TA muscles. IGF-I infusion resulted in significant increases in the total protein and DNA content of TA muscles (P < 0.05). As a result of these coordinated changes, the DNA-to-protein ratio of the hypertrophied TA was similar to that of the contralateral muscles. These results suggest that IGF-I may be acting to directly stimulate processes such as protein synthesis and satellite cell proliferation, which result in skeletal muscle hypertrophy.

  2. Morphometric analysis of muscle fibre types in rat locomotor and postural skeletal muscles in different stages of chronic kidney disease.

    PubMed

    Flisinski, M; Brymora, A; Elminowska-Wenda, G; Bogucka, J; Walasik, K; Stefanska, A; Strozecki, P; Manitius, J

    2014-08-01

    Muscle weakness and progressive loss of skeletal muscle mass are serious complications of chronic kidney disease (CKD). The pathogenesis of this condition is still poorly understood. The study investigated fibre type distribution and diameter in functionally different skeletal muscles: locomotor, gastrocnemius muscle (MG) and postural, longissimus thoracis muscle (ML) together with an evaluation of metabolic disturbances and nutritional parameters of rats with different stages of CKD. Wistar rats were randomized to a sham operation - CON, uninephrectomy - CKD1/2 or subtotal nephrectomy - CKD5/6. After 4 weeks, serum concentration haemoglobin (Hb), haptoglobin (Hp), MCP-1, advanced glycation end products (AGEs), and homocysteine (Hcy) were measured. Muscle specimens were stained for myofibrillary ATPase and NADH-diaphoreses activity according to Ziegan's method. There was a significant increase in the percentage of IID/X with a concomitant decrease of IIB fibres in ML in CKD1/2 vs. CON and CKD5/6. IIB fibre diameters in ML were smaller (53.4±7.3 vs. 58.1±8.1 and 59.8±11.2; p=0.08) for CKD5/6 vs. CKD1/2 and CON, respectively. There were significant differences for CKD5/6 and CKD1/2 vs. CON in: Hb (11.4±3.1; 13.7±0.7 and 14.1±1 g/dl), Hp (1.6±0.6; 1.6±0.6 and 0.7±0.4 mg/ml), AGEs (5.1±0.6; 4.3±1.2 and 4.6±0.9 AU), Hcy (7.2±1.2; 5.1±0.5 and 4.9±0.5 M), MCP-1 (609±255; 489±265 and 292±113 pg/ml), respectively. We concluded that early stages of CKD could induce the process of compensatory fast to slow fibre transformation, while in more advanced CKD this process may be blocked and atrophy of fast-twitch fibres may occur, predominantly in non-locomotor muscles. These disturbances can be secondary to CKD-related metabolic burden and inflammation.

  3. Fish protein intake induces fast-muscle hypertrophy and reduces liver lipids and serum glucose levels in rats.

    PubMed

    Kawabata, Fuminori; Mizushige, Takafumi; Uozumi, Keisuke; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kishida, Taro

    2015-01-01

    In our previous study, fish protein was proven to reduce serum lipids and body fat accumulation by skeletal muscle hypertrophy and enhancing basal energy expenditure in rats. In the present study, we examined the precise effects of fish protein intake on different skeletal muscle fiber types and metabolic gene expression of the muscle. Fish protein increased fast-twitch muscle weight, reduced liver triglycerides and serum glucose levels, compared with the casein diet after 6 or 8 weeks of feeding. Furthermore, fish protein upregulated the gene expressions of a fast-twitch muscle-type marker and a glucose transporter in the muscle. These results suggest that fish protein induces fast-muscle hypertrophy, and the enhancement of basal energy expenditure by muscle hypertrophy and the increase in muscle glucose uptake reduced liver lipids and serum glucose levels. The present results also imply that fish protein intake causes a slow-to-fast shift in muscle fiber type.

  4. Exercise-induced attenuation of obesity, hyperinsulinemia, and skeletal muscle lipid peroxidation in the OLETF rat.

    PubMed

    Morris, R Tyler; Laye, Matthew J; Lees, Simon J; Rector, R Scott; Thyfault, John P; Booth, Frank W

    2008-03-01

    The Otsuka Long-Evans Tokushima fatty (OLETF) rat is a model of hyperphagic obesity in which the animals retain the desire to run voluntarily. Running wheels were provided for 4-wk-old OLETF rats for 16 wk before they were killed 5 h (WL5), 53 h (WL53), or 173 h (WL173) after the wheels were locked. Sedentary (SED) OLETF rats that were not given access to running wheels served as age-matched cohorts. Epididymal fat pad mass, adipocyte volume, and adipocyte number were 58%, 39%, and 47% less, respectively, in WL5 than SED rats. Contrary to cessation of daily running in Fischer 344 x Brown Norway rats, epididymal fat did not increase during the first 173 h of running cessation in the OLETF runners. Serum insulin and glucose levels were 77% and 29% less, respectively, in WL5 than SED rats. Oil red O staining for intramyocellular lipid accumulation was not statistically different among groups. However, lipid peroxidation levels, as determined by total trans-4-hydroxy-2-nonenal (4-HNE) and 4-HNE normalized to oil red O, was higher in epitrochlearis muscles of SED than WL5, WL53, and WL173 rats. mRNA levels of glutathione S-transferase-alpha type 4, an enzyme involved in cellular defense against electrophilic compounds such as 4-HNE, were higher in epitrochlearis muscle of WL53 than WL173 and SED rats. In contrast, 4-HNE levels in omental fat were unaltered. Epitrochlearis muscle palmitate oxidation and relative transcript levels for peroxisome proliferator-activated receptor-delta and peroxisome proliferator-activated receptor-gamma coactivator type 1 were surprisingly not different between runners and SED rats. In summary, voluntary running was associated with lower levels of lipid peroxidation in skeletal muscle without significant changes in intramyocellular lipids or mitochondrial markers in OLETF rats at 20 wk of age. Therefore, even in a genetic animal model of extreme overeating, daily physical activity promotes improved health of skeletal muscle.

  5. Lipoxin A4 pretreatment mitigates skeletal muscle ischemia-reperfusion injury in rats

    PubMed Central

    Zong, Haiyang; Li, Xinghui; Lin, Haodong; Hou, Chunlin; Ma, Fenfen

    2017-01-01

    The aim of this study was to investigate the protective effects and underlying anti-oxidative molecular mechanism of lipoxin A4 (LA4) in rats with ischemia/reperfusion (I/R)-injured skeletal muscle. A rat model of I/R-injured skeletal muscle was obtained by subjecting rats to a 3-h ligation of the right femoral artery followed by 3 h of reperfusion. Treatment with LA4 significantly ameliorated histological damage scores in I/R-injured skeletal muscle. LA4 treatment resulted in remarkable decreases in the wet weight/dry weight ratio (W/D ratio), inflammatory response, oxidative stress, and cell apoptosis. In addition, treatment with LA4 was accompanied by a prominently enhanced nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and expression of heme oxygenase 1 (HO-1) in the I/R-injured skeletal muscle. However, these protective effects were reversed by zinc protoporphyrin-IX (ZnPP), a specific HO-1 inhibitor. Our study shows that LA4 may have the potential as a therapeutic agent for I/R-injured muscle tissue via activation of the Nrf2/HO-1 signaling pathway. PMID:28386340

  6. Targeted gene transfer into rat facial muscles by nanosecond pulsed laser-induced stress waves.

    PubMed

    Kurita, Akihiro; Matsunobu, Takeshi; Satoh, Yasushi; Ando, Takahiro; Sato, Shunichi; Obara, Minoru; Shiotani, Akihiro

    2011-09-01

    We investigate the feasibility of using nanosecond pulsed laser-induced stress waves (LISWs) for gene transfer into rat facial muscles. LISWs are generated by irradiating a black natural rubber disk placed on the target tissue with nanosecond pulsed laser light from the second harmonics (532 nm) of a Q-switched Nd:YAG laser, which is widely used in head and neck surgery and proven to be safe. After injection of plasmid deoxyribose nucleic acid (DNA) coding for Lac Z into rat facial muscles, pulsed laser is used to irradiate the laser target on the skin surface without incision or exposure of muscles. Lac Z expression is detected by X-gal staining of excised rat facial skin and muscles. Strong Lac Z expression is observed seven days after gene transfer, and sustained for up to 14 days. Gene transfer is achieved in facial muscles several millimeters deep from the surface. Gene expression is localized to the tissue exposed to LISWs. No tissue damage from LISWs is observed. LISW is a promising nonviral target gene transfer method because of its high spatial controllability, easy applicability, and minimal invasiveness. Gene transfer using LISW to produce therapeutic proteins such as growth factors could be used to treat nerve injury and paralysis.

  7. Targeted gene transfer into rat facial muscles by nanosecond pulsed laser-induced stress waves

    NASA Astrophysics Data System (ADS)

    Kurita, Akihiro; Matsunobu, Takeshi; Satoh, Yasushi; Ando, Takahiro; Sato, Shunichi; Obara, Minoru; Shiotani, Akihiro

    2011-09-01

    We investigate the feasibility of using nanosecond pulsed laser-induced stress waves (LISWs) for gene transfer into rat facial muscles. LISWs are generated by irradiating a black natural rubber disk placed on the target tissue with nanosecond pulsed laser light from the second harmonics (532 nm) of a Q-switched Nd:YAG laser, which is widely used in head and neck surgery and proven to be safe. After injection of plasmid deoxyribose nucleic acid (DNA) coding for Lac Z into rat facial muscles, pulsed laser is used to irradiate the laser target on the skin surface without incision or exposure of muscles. Lac Z expression is detected by X-gal staining of excised rat facial skin and muscles. Strong Lac Z expression is observed seven days after gene transfer, and sustained for up to 14 days. Gene transfer is achieved in facial muscles several millimeters deep from the surface. Gene expression is localized to the tissue exposed to LISWs. No tissue damage from LISWs is observed. LISW is a promising nonviral target gene transfer method because of its high spatial controllability, easy applicability, and minimal invasiveness. Gene transfer using LISW to produce therapeutic proteins such as growth factors could be used to treat nerve injury and paralysis.

  8. Branched-chain amino acid metabolism in rat muscle: abnormal regulation in acidosis

    SciTech Connect

    May, R.C.; Hara, Y.; Kelly, R.A.; Block, K.P.; Buse, M.G.; Mitch, W.E.

    1987-06-01

    Branched-chain amino acid (BCAA) metabolism is frequently abnormal in pathological conditions accompanied by chronic metabolic acidosis. To study how metabolic acidosis affects BCAA metabolism in muscle, rats were gavage fed a 14% protein diet with or without 4 mmol NH/sub 4/Cl x 100 g body wt/sup -1/ x day/sup -1/. Epitrochlearis muscles were incubated with L-(1-/sup 14/C)-valine and L-(1-/sup 14/C)leucine, and rates of decarboxylation, net transamination, and incorporation into muscle protein were measured. Plasma and muscle BCAA levels were lower in acidotic rats. Rates of valine and leucine decarboxylation and net transamination were higher in muscles from acidotic rats; these differences were associated with a 79% increase in the total activity of branched-chain ..cap alpha..-keto acid dehydrogenase and a 146% increase in the activated form of the enzyme. They conclude that acidosis affects the regulation of BCAA metabolism by enhancing flux through the transaminase and by directly stimulating oxidative catabolism through activation of branched-chain ..cap alpha..-keto acid dehydrogenase.

  9. Cryotherapy reduces skeletal muscle damage after ischemia/reperfusion in rats.

    PubMed

    Puntel, Gustavo O; Carvalho, Nélson R; Dobrachinski, Fernando; Salgueiro, Andréia C F; Puntel, Robson L; Folmer, Vanderlei; Barbosa, Nilda B V; Royes, Luiz F F; Rocha, João Batista T; Soares, Félix A A

    2013-02-01

    The aim of this study was to analyze the effects of cryotherapy on the biochemical and morphological changes in ischemic and reperfused (I/R) gastrocnemius muscle of rats. Forty male Wistar rats were divided into control and I/R groups, and divided based on whether or not the rats were submitted to cryotherapy. Following the reperfusion period, biochemical and morphological analyses were performed. Following cryotherapy, a reduction in thiobarbituric acid-reactive substances and dichlorofluorescein oxidation levels were observed in I/R muscle. Cryotherapy in I/R muscle also minimized effects such as decreased cellular viability, levels of non-protein thiols and calcium ATPase activity as well as increased catalase activity. Cryotherapy also limited mitochondrial dysfunction and decreased the presence of neutrophils in I/R muscle, an effect that was corroborated by reduced myeloperoxidase activity in I/R muscle treated with cryotherapy. The effects of cryotherapy are associated with a reduction in the intensity of the inflammatory response and also with a decrease in mitochondrial dysfunction.

  10. Effects of One Resistance Exercise Session on Vascular Smooth Muscle of Hypertensive Rats

    PubMed Central

    da Silva, Tharciano Luiz Teixeira Braga; Mota, Marcelo Mendonça; Fontes, Milene Tavares; Araújo, João Eliakim dos Santos; Carvalho, Vitor Oliveira; Bonjardim, Leonardo Rigoldi; Santos, Márcio Roberto Viana

    2015-01-01

    Background Hypertension is a public health problem and increases the incidence of cardiovascular diseases. Objective To evaluate the effects of a resistance exercise session on the contractile and relaxing mechanisms of vascular smooth muscle in mesenteric arteries of NG-nitro L-arginine methyl ester (L-NAME)-induced hypertensive rats. Methods Wistar rats were divided into three groups: control (C), hypertensive (H), and exercised hypertensive (EH). Hypertension was induced by administration of 20 mg/kg of L-NAME for 7 days prior to experimental protocols. The resistance exercise protocol consisted of 10 sets of 10 repetitions and intensity of 40% of one repetition maximum. The reactivity of vascular smooth muscle was evaluated by concentration‑response curves to phenylephrine (PHEN), potassium chloride (KCl) and sodium nitroprusside (SNP). Results Rats treated with L-NAME showed an increase (p < 0.001) in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) compared to the initial period of induction. No difference in PHEN sensitivity was observed between groups H and EH. Acute resistance exercise reduced (p < 0.001) the contractile response induced by KCl at concentrations of 40 and 60 mM in group EH. Greater (p < 0.01) smooth muscle sensitivity to NPS was observed in group EH as compared to group H. Conclusion One resistance exercise session reduces the contractile response induced by KCl in addition to increasing the sensitivity of smooth muscle to NO in mesenteric arteries of hypertensive rats. PMID:26107814

  11. Acute experimental colitis decreases colonic circular smooth muscle contractility in rats.

    PubMed

    Myers, B S; Martin, J S; Dempsey, D T; Parkman, H P; Thomas, R M; Ryan, J P

    1997-10-01

    Distal colitis decreases the contractility of the underlying circular smooth muscle. We examined how time after injury and lesion severity contribute to the decreased contractility and how colitis alters the calcium-handling properties of the affected muscle. Distal colitis was induced in rats by intrarectal administration of 4% acetic acid. Contractile responses to acetylcholine, increased extracellular potassium, and the G protein activator NaF were determined for circular muscle strips from sham control and colitic rats at days 1, 2, 3, 7, and 14 postenemas. Acetylcholine stimulation of tissues from day 3 colitic rats was performed in a zero calcium buffer, in the presence of nifedipine, and after depletion of intracellular stores of calcium. The colitis was graded macroscopically as mild, moderate, or severe. Regardless of agonist, maximal decrease in force developed 2 to 3 days posttreatment, followed by a gradual return to control by day 14. The inhibitory effect of colitis on contractility increased with increasing severity of inflammation. Limiting extracellular calcium influx had a greater inhibitory effect on tissues from colitic rats; intracellular calcium depletion had a greater inhibitory effect on tissues from control animals. The data suggest that both lesion severity and time after injury affect the contractile response of circular smooth muscle from the inflamed distal colon. Impaired utilization of intracellular calcium may contribute to the decreased contractility.

  12. High infectivity of Toxocara cati larvae from muscles of experimentally infected rats.

    PubMed

    Taira, Kensuke; Yanagida, Tomonori; Akazawa, Naoko; Saitoh, Yasuhide

    2013-09-23

    The organ distribution of Toxocara cati larvae in albino rats Rattus norvegicus (n=6/group) experimentally inoculated with 1000 embryonated eggs was examined 1, 2, 3, 7, 30, 90, and 180 days post inoculation (dpi), and the infectivity of recovered larvae was evaluated by bioassay in mice. The intestines, liver, lungs, muscles (carcass) and other organs (heart, brain, spleen, kidneys and genital organs) were digested for larval recovery. Larvae were recovered from all rats, with the mean number of recovered larvae ranging from 13.3 at 1 dpi to 135.6 at 90 dpi. Most of the larvae recovered were detected in the intestines (56.3%) and liver (43.8%) at 1 dpi; liver (21.6%) and lungs (69.6%) at 2 dpi; muscles (45.9%) and lungs (36.9%) at 3 dpi. Subsequently, most of larvae were recovered from muscles at 7 dpi (92.5%), 30 dpi (97.8%), 90 dpi (99.4%) and 180 dpi (99.1%). In the mouse bioassay, 43.8% of 90-day-old larvae and 43.0% of 180-day-old larvae recovered from rats established in mice. The present study demonstrated that T. cati larvae persist predominantly in rat muscles and nearly half of them retain infective for at least half a year. The results indicate that R. norvegicus may be a suitable paratenic host of T. cati under natural conditions.

  13. Effect of Tongue Exercise on Protrusive Force and Muscle Fiber Area in Aging Rats

    ERIC Educational Resources Information Center

    Connor, Nadine P.; Russell, John A.; Wang, Hao; Jackson, Michelle A.; Mann, Laura; Kluender, Keith

    2009-01-01

    Purpose: Age-related changes in tongue function may contribute to dysphagia in elderly people. The authors' purpose was to investigate whether aged rats that have undergone tongue exercise would manifest increased protrusive tongue forces and increased genioglossus (GG) muscle fiber cross-sectional areas. Method: Forty-eight young adult,…

  14. Dynamic Foot Stimulation Attenuates Soleus Muscle Atrophy Induced by Hindlimb Unloading in Rats

    NASA Technical Reports Server (NTRS)

    Kyparos, Antonios; Feeback, Daniel L.; Layne, Charles S.; Martinez, Daniel A.; Clarke, Mark S. F.

    2004-01-01

    Unloading-induced myofiber atrophy is a phenomenon that occurs in the aging population, bed-ridden patients and astronauts. The objective of this study was to determine whether or not dynamic foot stimulation (DFS) applied to the plantar surface of the rat foot can serve as a countermeasure to the soleus muscle atrophy normally observed in hindlimb unloaded (HU) rats. Thirty mature adult (6-month-old) male Wistar rats were randomly assigned into ambulatory control (AMB), hindlimb unloaded alone (HU), or hindlimb unloaded with the application of DFS (HU+DFS) groups. A dynamic pattern of pressure was applied to the right foot of each HU animal using a specially fabricated boot containing an inflatable air bladder connected to a solenoid air pump controlled by a laptop computer. The anti-atrophic effects of DFS were quantified morphometrically in frozen cross-sections of soleus muscle stained using the metachromatic-ATPase fiber typing technique. Application of DFS during HU significantly counteracted the atrophic response observed in the soleus by preventing approximately 85% of the reduction in Type I myofiber cross-sectional area (CSA) observed during HU. However, DFS did not protect type II fibers of the soleus from HU-induced atrophy or any fiber type in the soleus muscle of the contralateral control leg of the DFS-treated HU animals. These results illustrate that the application of DFS to the rat foot is an effective countermeasure to soleus muscle atrophy induced by HU.

  15. Nitric oxide pathways in circular muscle of the rat jejunum before and after small bowel transplantation.

    PubMed

    Balsiger, B M; Duenes, J A; Ohtani, N; Shibata, C; Farrugia, G; Anding, W J; Sarr, M G

    2000-01-01

    Previous studies suggest that nitric oxide synthase is upregulated after small bowel transplantation which may have implications in enteric dysfunction after small bowel transplantation. The aim of this study was to determine the role of nitric oxide in nonadrenergic, noncholinergic inhibitory function after small bowel transplantation in rat jejunal circular muscle. The following four groups of rats (n = >/=8 rats per group) were studied: Neurally intact control animals; 1 week after anesthesia and sham celiotomy, and either 1 week or 8 weeks after isogeneic, orthotopic small bowel transplantation. Full-thickness jejunal circular muscle strips were evaluated under isometric conditions for spontaneous contractile activity, response to electrical field stimulation, and effects of exogenous nitric oxide and nitric oxide antagonists. Spontaneous activity did not differ among groups. Electrical field stimulation inhibited activity similarly in all groups. Exogenous nitric oxide, NG-monomethyl L-arginine monoacetate salt (a nitric oxide synthase inhibitor), and methylene blue (cGMP antagonist) had no effect on spontaneous activity. Neither nitric oxide antagonist altered the inhibitory response to neural excitation by electrical field stimulation in any group. Nitric oxide, a known inhibitory neurotransmitter in other gut smooth muscle, has no apparent role in rat jejunal circular muscle before or after small bowel transplantation.

  16. The upstream muscle-specific enhancer of the rat muscle creatine kinase gene is composed of multiple elements.

    PubMed Central

    Horlick, R A; Benfield, P A

    1989-01-01

    A series of constructs that links the rat muscle creatine kinase promoter to the bacterial chloramphenicol acetyltransferase gene was generated. These constructs were introduced into differentiating mouse C2C12 myogenic cells to localize sequences that are important for up-regulation of the creatine kinase gene during myogenic differentiation. A muscle-specific enhancer element responsible for induction of chloramphenicol acetyltransferase expression during myogenesis was localized to a 159-base-pair region from 1,031 to 1,190 base pairs upstream of the transcription start site. Analysis of transient expression experiments using promoters mutated by deletion indicated the presence of multiple functional domains within this muscle-specific regulatory element. A DNA fragment spanning this region was used in DNase I protection experiments. Nuclear extracts derived from C2 myotubes protected three regions (designated E1, E2, and E3) on this fragment from digestion, which indicated there may be three or more trans-acting factors that interact with the creatine kinase muscle enhancer. Gel retardation assays revealed that factors able to bind specifically to E1, E2, and E3 are present in a wide variety of tissues and cell types. Transient expression assays demonstrated that elements in regions E1 and E3, but not necessarily E2, are required for full enhancer activity. Images PMID:2761536

  17. Atrophy and growth failure of rat hindlimb muscles in tail-cast suspension

    NASA Technical Reports Server (NTRS)

    Jaspers, S. R.; Tischler, M. E.

    1984-01-01

    The primary objective of the present study is related to an evaluation of a modified tail-cast suspension model as a means of identifying metabolic factors which control or are associated with muscle atrophy and growth failure. Two different control conditions (normal and tail-casted weight bearing) were studied to determine the appropriate control for tail-cast suspension. A description is presented of a model which is most useful for studying atrophy of hindlimb muscles under certain conditions. Female Sprague-Dawley rats were employed in the experiments. Attention is given to growth rate and urinary excretion of urea and ammonia in different types of rats, the relationship between body weight and skeletal muscle weight, and the relationship between animal body weight and rates of protein synthesis and protein degradation.

  18. Response of rat hindlimb muscles to 12 hours recovery from tail-cast suspension

    NASA Technical Reports Server (NTRS)

    Tischler, M. E.; Henriksen, E. J.; Jacob, S.; Cook, P.; Jaspers, S.

    1985-01-01

    Previous work has shown a number of biochemical changes which accompany atrophy or reduced muscle growth in hindlimb of tail-casted, suspended rats. These results clearly show that altered muscle growth was due to changes in protein turnover. Accordingly, the rise in soleus tyrosine following unloading reflects the more negative protein balance. Other major changes we found included slower synthesis of glutamine as indicated by lower ratios of glutamine/glutamate and reduced levels of aspartate which coincide with slower aspartate and ammonia metabolism in vitro. In conjunction with the study of SL-3 rats, which were subjected to 12 h of post-flight gravity, a study of the effects of 12 h eight bearing on metabolism of 6-day unloaded hindlimb muscles was carried out.

  19. Heart failure alters matrix metalloproteinase gene expression and activity in rat skeletal muscle.

    PubMed

    Carvalho, Robson Francisco; Dariolli, Rafael; Justulin Junior, Luis Antonio; Sugizaki, Mário Mateus; Politi Okoshi, Marina; Cicogna, Antonio Carlos; Felisbino, Sérgio Luis; Dal Pai-Silva, Maeli

    2006-12-01

    Heart failure is associated with a skeletal muscle myopathy with cellular and extracellular alterations. The hypothesis of this investigation is that extracellular changes may be associated with enhanced mRNA expression and activity of matrix metalloproteinases (MMP). We examined MMP mRNA expression and MMP activity in Soleus (SOL), extensor digitorum longus (EDL), and diaphragm (DIA) muscles of young Wistar rat with monocrotaline-induced heart failure. Rats injected with saline served as age-matched controls. MMP2 and MMP9 mRNA contents were determined by RT-PCR and MMP activity by electrophoresis in gelatin-containing polyacrylamide gels in the presence of SDS under non-reducing conditions. Heart failure increased MMP9 mRNA expression and activity in SOL, EDL and DIA and MMP2 mRNA expression in DIA. These results suggest that MMP changes may contribute to the skeletal muscle myopathy during heart failure.

  20. Metformin, but not exercise training, increases insulin responsiveness in skeletal muscle of Sprague-Dawley rats.

    PubMed

    Borst, S E; Snellen, H G

    2001-08-17

    We assessed the effects of combined metformin treatment and exercise training on body composition, on insulin concentration following glucose loading, on insulin-stimulated glucose transport in skeletal muscle, and on muscle glycogen content. Male Sprague-Dawley rats were treated for 35 days with or without metformin (320 mg/kg/day) and/or treadmill exercise training (20 min at 20 m/min, 5 days/wk). Because metformin reduces food intake, pair-fed controls were included. Metformin, training, and pair-feeding all decreased food intake, body weight, and insulin concentration following glucose loading. Metformin and training reduced intra-abdominal fat, but pair feeding did not. In isolated strips derived from soleus, epitrochlearis and extensor carpi ulnaris muscles, metformin increased insulin-stimulated transport of [3H]-2-deoxyglucose by 90%, 89% and 125%, respectively (P < 0.02) and training increased [3H]-2-deoxyglucose transport in the extensor carpi ulnaris muscle only (66%, P < 0.05). Pair-feeding did not alter [3H]-2-deoxyglucose transport. Training increased gastrocnemius muscle glycogen by 100% (P < 0.001). Metformin and pair-feeding did not alter muscle glycogen. We conclude that metformin reverses the maturation-induced impairment of insulin responsiveness in Sprague-Dawley rats by increasing insulin-stimulated glucose transport in skeletal muscle and that this effect is not secondary to reduced food intake. We also conclude that metformin and exercise training may increase insulin sensitivity by different mechanisms, with training causing increased glucose transport only in some muscles and also causing increased muscle glycogen storage.

  1. Heterogeneity of fiber characteristics in the rat masseter and digastric muscles.

    PubMed

    Sano, R; Tanaka, E; Korfage, J A M; Langenbach, G E J; Kawai, Nobuhiko; van Eijden, T M G J; Tanne, K

    2007-10-01

    The functional requirements in muscle use are related to the fiber type composition of the muscles and the cross-sectional area of the individual fibers. We investigated the heterogeneity in the fiber type composition and fiber cross-sectional area in two muscles with an opposing function, namely the digastric and masseter muscles (n = 5 for each muscle) of adult male rats, by means of immunohistochemical staining according to their myosin heavy chain (MyHC) content. The digastric and masseter muscles were taken from Wistar strain male rats 10 weeks old. In the masseter six predefined sample locations were examined; in the digastric four. Most regions showed dominant proportions of type IIA and IIX fibers. However, both muscles also revealed a regional heterogeneity in their fiber type distribution. In the digastric, type I fibers were detected only at the central and deep areas of the anterior and posterior belly, respectively. Meanwhile, the peripheral area of the anterior belly contained a higher proportion of type IIB fibers. In the masseter, the type I fibers were absent. In the superficial masseter the distribution of IIA and IIB fibers was significantly different between the superior and inferior regions. In the deep masseter, regional differences were observed among all four examined areas, of which the posterolateral region contained the highest proportion of type IIB fibers. The cross-sectional areas of type IIB fibers were always the largest, followed by the type IIX and IIA fibers. Only a few differences in cross-sectional area of corresponding fiber types were detected between the various sites. In conclusion, the masseter and digastric muscles showed an obvious heterogeneity of fiber type composition and fiber cross-sectional area. Their heterogeneity reflects the complex role of the both muscles during function. This detailed description of the fiber type composition can serve as a reference for future studies examining the muscular adaptations after

  2. Effect of pulsed and continuous therapeutic ultrasound on healthy skeletal muscle in rats

    PubMed Central

    Vásquez, Bélgica; Navarrete, Javiera; Farfán, Emilio; Cantín, Mario

    2014-01-01

    Ultrasound therapy is used to treat injuries in joints, nerves and tendons. Part of the radiation generated is absorbed by nearby undamaged tissues, such as muscles. The aim was to evaluate histomorphological changes in the healthy gastrocnemius muscle in rats irradiated with continuous ultrasound (CUS) and pulsed ultrasound (PUS). Healthy adult rats were used, separated into two groups: CUS and PUS. Both were irradiated in the gastrocnemius muscle for 10 days: the CUS group in continuous mode (3 MHz, 1.0 W/cm2, 1 min/session) and the PUS group in pulsed mode (3 MHz, 1.0 W/cm2, 100 Hz, 50% duty cycle, 1 min/session). The contralateral muscles were used as a control. Their histological characteristics were analyzed, and the area and perimeter of the muscle fibers were measured. The connective tissue showed no histological changes. The area of muscle fibers of the irradiated groups was significantly greater (CUS 1325.2±182.1 μm2, p=0.0278 and PUS 1019.4±125.3 μm2, p=0.0398) than the control, and the CUS area was greater than the PUS (p=0.0383). The perimeter of muscle fibers showed significant differences between the irradiated groups (CUS 148±11.12 μm, p=0.0178 and PUS 129.3±8.83 μm, p=0.0236) compared to the control, as well as differences between CUS and PUS (p=0.0319). The application of ultrasound on healthy muscle produces hypertrophy of the muscle fibers, greater when continuous mode is used. It is advisable to apply pulsed, focused ultrasound therapies with sound heads sufficient for the tissue or zone to be treated, thereby reducing the risk of altering the adjacent healthy tissue. PMID:24551303

  3. Molecular regulation of apoptosis in fast plantaris muscles of aged rats.

    PubMed

    Pistilli, Emidio E; Siu, Parco M; Alway, Stephen E

    2006-03-01

    This study tested the hypothesis that aging exacerbates apoptotic signaling in rat fast plantaris muscle during muscle unloading. Plantaris muscle mass was 22% lower in aged animals and the apoptotic index was 600% higher, when compared to those in young adult animals. Following 14 days of hind-limb unloading, absolute plantaris muscle mass was 20% lower in young adult animals with a corresponding 200% higher elevation of the apoptotic index. Unloading had no affect on muscle weight or apoptotic index of aged plantaris muscles. The changes in pro-apoptotic messenger RNA (mRNA) for apoptotic protease activating factor-1 (Apaf-1), Bax, and inhibitor of differentiation protein-2 (Id2) were exacerbated with aging. Bax and Bcl-2 protein levels were also altered differently in aged muscle, compared to young. Significant positive correlations were observed between the changes in Id2 and Bax mRNA, and Id2 and caspase-9 mRNA. These data suggest that a pro-apoptotic environment may contribute to aging-associated atrophy in fast skeletal muscle, but apoptotic signaling differs by age.

  4. Membrane lipid rafts disturbance in the response of rat skeletal muscle to short-term disuse.

    PubMed

    Petrov, Alexey M; Kravtsova, Violetta V; Matchkov, Vladimir V; Vasiliev, Alexander N; Zefirov, Andrey L; Chibalin, Alexander V; Heiny, Judith A; Krivoi, Igor I

    2017-03-08

    Marked loss of skeletal muscle mass occurs under various conditions of disuse, but the molecular and cellular mechanisms leading to atrophy are not completely understood. We investigate early molecular events which might play a role in skeletal muscle remodeling during mechanical unloading (disuse). The effects of acute (6 - 12 h) hindlimb suspension on the soleus muscles from adult rats were examined. The integrity of plasma membrane lipid rafts was tested utilizing cholera toxin B subunit, or fluorescent sterols. In addition, resting intracellular Ca(2+) level was analyzed. Acute disuse disturbed the plasma membrane lipid-ordered phase throughout the sarcolemma and was more pronounced in junctional membrane regions. Ouabain (1 µM), which specifically inhibits the Na,K-ATPase α2 isozyme in rodent skeletal muscles, produced similar lipid rafts changes in control muscles, but was ineffective in suspended muscles, which show an initial loss of α2 Na,K-ATPase activity. Lipid rafts were able to recover with cholesterol supplementation, suggesting that disturbance results from cholesterol loss. Repetitive nerve stimulation also restores lipid rafts, specifically in junctional sarcolemma region. Disuse locally lowered the resting intracellular Ca(2+) concentration only near the neuromuscular junction of muscle fibers. Our results provide the evidence to suggest that the ordering of lipid rafts strongly depends on motor nerve input and may involve interactions with the α2 Na,K-ATPase. Lipid rafts disturbance, accompanied by intracellular Ca(2+) dysregulation are among the earliest remodeling events induced by skeletal muscle disuse.

  5. Time course of IL-15 expression after acute resistance exercise in trained rats: effect of diabetes and skeletal muscle phenotype.

    PubMed

    Molanouri Shamsi, Mahdieh; Hassan, Zuhair Mohammad; Quinn, LeBris S; Gharakhanlou, Reza; Baghersad, Leila; Mahdavi, Mehdi

    2015-06-01

    Type 1 diabetes is associated with skeletal muscle atrophy. Skeletal muscle is an endocrine organ producing myokines such as interleukin-15 (IL-15) and interleukin-6 (IL-6) in response to contraction. These factors may mediate the effects of exercise on skeletal muscle metabolism and anabolic pathways. Lack of correlation between muscle IL-15 mRNA and protein levels after exercise training has been observed, while regulatory effects of IL-6 on IL-15 expression have also been suggested. This study determined post-exercise changes in muscle IL-15 and IL-6 mRNA expression and IL-15 protein levels in healthy and streptozotocin-induced diabetic rats in both the fast flexor hallucis longus (FHL) and slow soleus muscles. Resistance training preserved FHL muscle weight in diabetic rats and increased IL-15 protein levels in both the soleus and FHL muscles. However, the temporal pattern of this response was distinct in normal and diabetic rats. Moreover, discordance between post-exercise muscle IL-15 mRNA and protein expression was observed in our study, and diabetes suppressed post-exercise increases in FHL muscle IL-6 mRNA expression. Our study indicates that training, skeletal muscle phenotype, and metabolic status all influence the temporal pattern of post-exercise changes in IL-15 expression. Muscle IL-15 protein levels increase following training, suggesting this may be an adaptation contributing to increased capacity for secretion of this myokine that is not depressed by the diabetic state.

  6. Branched-chain amino acid-rich diet improves skeletal muscle wasting caused by cigarette smoke in rats.

    PubMed

    Tomoda, Koichi; Kubo, Kaoru; Hino, Kazuo; Kondoh, Yasunori; Nishii, Yasue; Koyama, Noriko; Yamamoto, Yoshifumi; Yoshikawa, Masanori; Kimura, Hiroshi

    2014-04-01

    Cigarette smoke induces skeletal muscle wasting by a mechanism not yet fully elucidated. Branched-chain amino acids (BCAA) in the skeletal muscles are useful energy sources during exercise or systemic stresses. We investigated the relationship between skeletal muscle wasting caused by cigarette smoke and changes in BCAA levels in the plasma and skeletal muscles of rats. Furthermore, the effects of BCAA-rich diet on muscle wasting caused by cigarette smoke were also investigated. Wistar Kyoto (WKY) rats that were fed with a control or a BCAA-rich diet were exposed to cigarette smoke for four weeks. After the exposure, the skeletal muscle weight and BCAA levels in plasma and the skeletal muscles were measured. Cigarette smoke significantly decreased the skeletal muscle weight and BCAA levels in both plasma and skeletal muscles, while a BCAA-rich diet increased the skeletal muscle weight and BCAA levels in both plasma and skeletal muscles that had decreased by cigarette smoke exposure. In conclusion, skeletal muscle wasting caused by cigarette smoke was related to the decrease of BCAA levels in the skeletal muscles, while a BCAA-rich diet may improve cases of cigarette smoke-induced skeletal muscle wasting.

  7. Muscle mechanical properties of adult and older rats submitted to exercise after immobilization

    PubMed Central

    Kodama, Fábio Yoshikazu; Camargo, Regina Celi Trindade; Job, Aldo Eloizo; Ozaki, Guilherme Akio Tamura; Koike, Tatiana Emy; Camargo Filho, José Carlos Silva

    2012-01-01

    Objectives To describe the effects of immobilization, free remobilization and remobilization by physical exercise about mechanical properties of skeletal muscle of rats of two age groups. Methods 56 Wistar rats divided into two groups according to age, an adult group (five months) and an older group (15 months). These groups were subdivided in: control, immobilized, free remobilized and remobilized by physical exercise. The pelvic limb of rats was immobilized for seven days. The exercise protocol consisted of five swimming sessions, once per day and 25 minutes per session. The gastrocnemius muscle was subjected to tensile tests, and evaluated the properties: load at the maximum limit, stretching at the maximum limit and stiffness. Results The immobilization reduced the values of load at the maximum limit and the remobilization protocols were not sufficient to restore control levels in adult group and older rats. The stretching at the maximum limit differs only in the older group. Conclusions The immobilization reduces the muscle's ability to bear loads and exercise protocol tends to restore the default at control values in adult and older rats. The age factor only interfered in the stretching at the maximum limit, inducing a reduction of this property in the post-immobilization. Level of Evidence II, Investigating the Results of Treatment. PMID:24453606

  8. Succinylcholine-induced hyperkalemia in the rat following radiation injury to muscle. [60Co

    SciTech Connect

    Cairoli, V.J.; Ivankovich, A.D.; Vucicevic, D.; Patel, K.

    1982-02-01

    During anesthetic preparation of a patient who had received routine radiation therapy of sarcoma of the leg, cardiac collapse occurred following succinylcholine (SCh) administration. Experiments were designed to test the hypothesis that radiation injury to muscle might cause increased sensitivity to SCh similar to that reported in patients with muscle trauma, severe burns, and lesions causing muscle denervation. Venous plasma potassium levels and arterial blood gas tensions were measured in rats after they were given SCh (3 mg/kg) at various times following 60Co irradiation of the hind legs. Nonirradiated rats responded to SCh with a slight but statistically significant increase in plasma K+. Rats subjected to high levels of radiation (10,000 to 20,000 R) and given SCh 4 to 7 days later responded in the same way as the control rats. Plasma K+ levels in rats exposed to a fractionated irradiated dosage (25000 R given twice with a 1-week interval) followed by SCh 1 week later were similar to those in the control group, but when SCh was given 2 weeks later (3 weeks after initial irradiation) there was a marked elevation of plasma K+, from 3.6 to 7.7 meq/L, a statistically significant increase.

  9. Succinylcholine-induced hyperkalemia in the rat following radiation injury to muscle

    SciTech Connect

    Cairoli, V.J.; Ivankovich, A.D.; Vucicevic, D.; Patel, K.

    1982-02-01

    During anesthetic preparation of a patient who had received routine radiation therapy for sarcoma of the leg, cardiac collapse occurred following succinylcholine (SCh) administration. Experiments were designed to test the hypothesis that radiation injury to muscle might cause increased sensitivity to SCh similar to that reported in patients with muscle trauma, severe burns, and lesions causing muscle denervation. Venous plasma potassium levels and arterial blood gas tensions were measured in rats after they were given SCh (3 mg/kg) at various times following /sup 60/Co irradiation of the hind legs. Nonirradiated rats responded to SCh with a slight but statistically significant increase in plasma K+. Rats subjected to high levels of radiation (10,000 to 20,000 R) and given SCh 4 to 7 days later responded in the same way as the control rats. Plasma K+ levels in rats exposed to a fractionated irradiated dosage (2500 R given twice with a 1-week interval) followed by SCh 1 week later were similar to those in the control group, but when SCh was given 2 weeks later (3 weeks after initial irradiation) there was a marked elevation of plasma K+, from 3.6 to 7.7 meq/L, a statistically significant increase.

  10. Insulin receptor binding and protein kinase activity in muscles of trained rats

    SciTech Connect

    Dohm, G.L.; Sinha, M.K.; Caro, J.F.

    1987-02-01

    Exercise has been shown to increase insulin sensitivity, and muscle is quantitatively the most important tissue of insulin action. Since the first step in insulin action is the binding to a membrane receptor, the authors postulated that exercise training would change insulin receptors in muscle and in this study they have investigated this hypothesis. Female rats initially weighing approx. 100 g were trained by treadmill running for 2 h/day, 6 days/wk for 4 wk at 25 m/min (0 grade). Insulin receptors from vastus intermedius muscles were solubilized by homogenizing in a buffer containing 1% Triton X-100 and then partially purified by passing the soluble extract over a wheat germ agglutinin column. The 4 wk training regimen resulted in a 65% increase in citrate synthase activity in red vastus lateralis muscle, indicating an adaptation to exercise ( SVI). Insulin binding by the partially purified receptor preparations was approximately doubled in muscle of trained rats at all insulin concentrations, suggesting an increase in the number of receptors. Training did not alter insulin receptor structure as evidenced by electrophoretic mobility under reducing and nonreducing conditions. Basal insulin receptor protein kinase activity was higher in trained than untrained animals and this was likely due to the greater number of receptors. However, insulin stimulation of the protein kinase activity was depressed by training. These results demonstrate that endurance training does alter receptor number and function in muscle and these changes may be important in increasing insulin sensitivity after exercise training.

  11. Coupling of albumin flux to volume flow in skin and muscles of anesthetized rats

    SciTech Connect

    Renkin, E.M.; Gustafson-Sgro, M.; Sibley, L.

    1988-09-01

    Bovine serum albumin (BSA) labeled with /sup 131/I or /sup 125/I was injected intravenously in pentobarbital sodium-anesthetized rats, and tracer clearances into leg skin and muscles were measured over 30, 60, and 120 min. BSA labeled with the alternate tracer was used as vascular volume reference. Two minutes before injection of the tracer, a ligature was tied around one femoral vein to occlude outflow partially and raise capillary pressure in that leg. The unoccluded leg served as control. Skin and muscles of the occluded leg had variably and substantially higher water contents (delta W) than paired control tissues and slightly but consistently increased albumin clearances (CA). The delta CA/delta W, equivalent to the albumin concentration of capillary filtrate relative to plasma determined by linear regression, were as follows: leg skin 0.004 (95% confidence limits -0.001 to +0.009), muscle biceps femoris 0.005 (0.001-0.010), muscle gastrocnemius 0.011 (0.004-0.019), muscle tibialis anterior 0.016 (0.012-0.021). All these values are significantly less than 0.10, which corresponds to a reflection coefficient for serum albumin (sigma A) of 0.90. Convective coupling of albumin flux to volume flux in skin and muscles of intact, anesthetized rats is low, with sigma AS in the range 0.98 to greater than 0.99.

  12. [Method of isolation of intrafusal fibres of muscle spindle in soleus of rats].

    PubMed

    Zhao, Xue-Hong; Fan, Xiao-Li; Liu, Guang-Bin

    2013-08-25

    Capsule restricts the further study on muscle spindle function and the involved mechanism. The aim of this study was to establish the isolation method of intrafusal fibres from the isolated rat muscle spindle. Intrafusal fibres were harvested from muscle spindle of soleus muscle in rats using neutrase-collagenase digestion. A variety of incubation mediums have been tested to find out an appropriate medium of intrafusal fibers in vitro. Trypan blue staining was used to detect cell death, and patch clamp was used to record resting potential. The results showed that the intrafusal fibres incubated with amine acid-saline solution were almost all dead. DMEM could maintain good condition of the fibres, but excess CO2 ventilation would induce cellular swelling or even death. While Leiboviz's 15 (L-15) medium can guarantee 1-2 h of physiological condition of the intrafusal fibres. Coverslips treated with gelatin, polylysine and serum was the better interfaces for the intrafusal fibres to adhere easily, compared with regularly treated coverslip. The resting potential of intrafusal fibres was (-45.3 ± 5.1) mV, consistent with others obtained from in vivo muscle spindle from cats and frogs. These results suggest that the isolation method of the intrafusal fibres has been successfully established in the present study, providing a new approach in better understanding of muscle spindle activities and the involved mechanism.

  13. Effect of the Lipoxygenase Inhibitor Baicalein on Muscles in Ovariectomized Rats

    PubMed Central

    Kling, J. H.; Kosinsky, R. L.; Hoffmann, D. B.; Komrakova, M.; Wicke, M.; Menger, B.; Sehmisch, S.

    2016-01-01

    Sarcopenia, a loss of muscle mass accompanying osteoporosis, leads to falls and fall-related injuries. Baicalein, as a phytochemical agent, has an antioxidative and anti-inflammatory effect in muscle. In this study, sixty-one female Sprague Dawley rats were divided into five groups: four groups were ovariectomized (OVX) and one control group was nonovariectomized (NON-OVX). Eight weeks after ovariectomy, three disparate concentrations (1 mg/kg body weight (BW), 10 mg/kg BW, and 100 mg/kg BW) of baicalein were applied subcutaneously daily in three OVX groups. Mm. soleus, gastrocnemius, and longissimus were extracted; their diameter, area, relation to body, and muscle weights as well as number of capillaries per fibre were recorded. In Mm. soleus and gastrocnemius, the baicalein effect (increasing number of capillaries per fibre) was proportional to the dose applied. The fibre diameters and area under baicalein treatment were significantly greater compared to OVX and NON-OVX groups. In M. longissimus, we observed a shift to type IIa fibres. Serum creatine kinase levels were significantly lower in highest baicalein concentration group. We conclude that baicalein can stimulate angiogenesis, though not fibre type-specific, in skeletal muscle and reduce the estrogen-related loss of fibre diameter and area in the skeletal muscle in rats. Therefore, a protective effect of baicalein on muscle cells can be assumed. PMID:28050282

  14. Role for monocyte chemoattractant protein-1 in the induction of chronic muscle pain in the rat.

    PubMed

    Alvarez, Pedro; Green, Paul G; Levine, Jon D

    2014-06-01

    While raised levels of monocyte chemoattractant protein 1 (MCP-1) have been observed in patients with chronic muscle pain, direct evidence for its role as an algogen in skeletal muscle is still lacking. In the rat, MCP-1 induces a dose-dependent mechanical hyperalgesia lasting for up to 6weeks. Following recovery, rats exhibited a markedly prolonged hyperalgesia to an intramuscular injection of prostaglandin E2, hyperalgesic priming. Intrathecal pretreatment with isolectin B4 (IB4)-saporin, which selectively destroys IB4-positive (IB4+) nociceptors, markedly decreased MCP-1-induced hyperalgesia and prevented the subsequent development of priming. To evaluate the involvement of MCP-1 in stress-induced chronic pain we administered, intrathecally, antisense (AS) or mismatch oligodeoxynucleotides directed against CCR2 (the canonical receptor for MCP-1) mRNA, during the exposure to water-avoidance stress, a model of stress-induced persistent muscle pain. The AS treatment attenuated this hyperalgesia, whereas IB4-saporin abolished water-avoidance stress-induced muscle hyperalgesia and prevented stress-induced hyperalgesic priming. These results indicate that MCP-1 induces persistent muscle hyperalgesia and a state of latent chronic sensitization to other algogens, by action on its cognate receptor on IB4+ nociceptors. Because MCP-1 also contributes to stress-induced widespread chronic muscle pain, it should be considered as a player in chronic musculoskeletal pain syndromes.

  15. Extraocular muscle degeneration and regeneration after exposure of rats to incandescent radiant energy.

    PubMed

    O'Steen, W K; Shear, C R; Anderson, K V

    1975-06-01

    Exposure of albino rats to incandescent radiant energy for a short period of time in an elevated environmental temperature (39 degrees C) causes degenerative changes in the extraocular muscles. The muscle fibres regenerate and the muscles reorganize if the animals are returned to room lighting and temperature. Extraocular muscles (EOMs) were damaged first near their insertion on the eyeball. All EOMs of both eyes were affected, but the degeneration did not extend the entire length of the muscle. The peripheral fibres of each muscle were damaged before the more central fibres. Mitochondria were swollen and often contained dense bodies. Numerous vesicular profiles, possibly from the sarcotubular system, were present. Myofibrils of the more severely damaged fibres lacked typical Z-disk structures, and I-bands had disappeared by 24 h after the exposure period, a degenerative pattern which seems to be unique for this method of EOM damage. EOM degeneration appeared to be dependent on the interaction between thermal and radiant energy on the orbital contents. However, EOMs were only rarely and very slightly affected when rats were exposed to elevated temperature in the absence of incandescent radiant energy. When an opaque, black, ocular occluder was placed over one eye and the contralateral eye was left unoccluded, EOMs and retinas of occluded eyes were undamaged, while those tissues were severely damaged in unoccluded eyes. Therefore, the most critical single variable in inducing EOM degeneration appears to be exposure to radiant energy.

  16. Changes in the cholinergic system of rat sciatic nerve and skeletal muscle following suspension induced disuse

    NASA Technical Reports Server (NTRS)

    Gupta, R. C.; Misulis, K. E.; Dettbarn, W. D.

    1984-01-01

    Muscle disused induced changes in the cholinergic system of sciatic nerve, slow twitch soleus (SOL) and fast twitch extensor digitorum longus (EDL) muscle were studied in rats. Rats with hindlimbs suspended for 2 to 3 weeks showed marked elevation in the activity of choline acetyltransferase (ChAT) in sciatic nerve (38%), in SOL (108%) and in EDL (67%). Acetylcholinesterase (AChE) activity in SOL increased by 163% without changing the molecular forms pattern of 4S, 10S, 12S, and 16S. No significant changes in activity and molecular forms pattern of AChE were seen in EDL or in AChE activity of sciatic nerve. Nicotinic receptor binding of 3H-acetylcholine was increased in both muscles. When measured after 3 weeks of hindlimb suspension the normal distribution of type 1 fibers in SOL was reduced and a corresponding increase in type IIa and IIb fibers is seen. In EDL no significant change in fiber proportion is observed. Muscle activity, such as loadbearing, appears to have a greater controlling influence on the characteristics of the slow twitch SOL muscle than upon the fast twitch EDL muscle.

  17. Receptor Expression in Rat Skeletal Muscle Cell Cultures

    NASA Technical Reports Server (NTRS)

    Young, Ronald B.

    1996-01-01

    One on the most persistent problems with long-term space flight is atrophy of skeletal muscles. Skeletal muscle is unique as a tissue in the body in that its ability to undergo atrophy or hypertrophy is controlled exclusively by cues from the extracellular environment. The mechanism of communication between muscle cells and their environment is through a group of membrane-bound and soluble receptors, each of which carries out unique, but often interrelated, functions. The primary receptors include acetyl choline receptors, beta-adrenergic receptors, glucocorticoid receptors, insulin receptors, growth hormone (i.e., somatotropin) receptors, insulin-like growth factor receptors, and steroid receptors. This project has been initiated to develop an integrated approach toward muscle atrophy and hypertrophy that takes into account information on the populations of the entire group of receptors (and their respective hormone concentrations), and it is hypothesized that this information can form the basis for a predictive computer model for muscle atrophy and hypertrophy. The conceptual basis for this project is illustrated in the figure below. The individual receptors are shown as membrane-bound, with the exception of the glucocorticoid receptor which is a soluble intracellular receptor. Each of these receptors has an extracellular signalling component (e.g., innervation, glucocorticoids, epinephrine, etc.), and following the interaction of the extracellular component with the receptor itself, an intracellular signal is generated. Each of these intracellular signals is unique in its own way; however, they are often interrelated.

  18. Stress in the Adult Rat Exacerbates Muscle Pain Induced by Early-Life Stress

    PubMed Central

    Alvarez, Pedro; Green, Paul G.; Levine, Jon D.

    2013-01-01

    Background Early-life stress and exposure to stressful stimuli play a major role in the development of chronic widespread pain in adults. However, how they interact in chronic pain syndromes remains unclear. Methods Dams and neonatal litters were submitted to a restriction of nesting material (neonatal limited bedding, NLB) for one week. As adults, these rats were exposed to a painless sound stress protocol. The involvement of sympathoadrenal catecholamines, interleukin 6 (IL-6) and tumor necrosis alpha (TNFα) in nociception, was evaluated through of behavioral and ELISA assays, surgical interventions and intrathecal antisense treatments. Results Adult NLB rats exhibited mild muscle hyperalgesia, which was markedly aggravated by sound stress (peaking 15 days after exposure). Adrenal medullectomy did not modify hyperalgesia in NLB rats but prevented its aggravation by sound stress. Sustained administration of epinephrine to NLB rats mimicked sound stress effect. Intrathecal treatment with antisense directed to IL-6-receptor subunit gp130, but not to TNFα type 1 receptor (TNFR1), inhibited hyperalgesia in NLB rats. However, antisense against either gp130 or TNFR1 inhibited sound stress-induced enhancement of hyperalgesia. Compared to control rats, NLB rats exhibit increased plasma levels of IL-6 but decreased levels of TNFα, whereas sound stress increases IL-6 plasma levels in control but not in NLB rats. Conclusions Early-life stress induces a persistent elevation of IL-6, hyperalgesia and susceptibility to chronic muscle pain, which is unveiled by exposure to stress in adults. This probably depends on an interaction between adrenal catecholamines and pro-inflammatory cytokines acting at muscle nociceptor level. PMID:23706525

  19. Age-dependent Muscle Adaptation after Chronic Stretch-shortening Contractions in Rats.

    PubMed

    Rader, Erik P; Layner, KaylaN; Triscuit, Alyssa M; Chetlin, Robert D; Ensey, James; Baker, Brent A

    2016-01-01

    Age-related differences in contraction-induced adaptation have been well characterized especially for young and old rodent models but much less so at intermediate ages. Therefore, additional research is warranted to determine to what extent alterations in adaptation are due to maturation versus aging per se. The purpose of our study was to evaluate muscles of Fisher 344XBrown Norway rats of various ages following one month of exposure to stretch-shortening contractions (SSCs). With exposure, muscles mass increased by ~10% for 27 and 30 month old rats vs. ~20% for 3 and 6 month old rats (P < 0.05). For 3 month old rats, maximum isometric force and dynamic peak force increased by 22 ± 8% and 27 ± 10%, respectively (P < 0.05). For 6 month old rats, these forces were unaltered by exposure and positive work capacity diminished by 27 ± 2% (P = 0.006). By 30 months of age, age-related deficits in maximum isometric force, peak force, negative work, and positive work were apparent and SSC exposure was ineffective at counteracting such deficits. Recovery from fatigue was also tested and exposure-induced improvements in fatigue recovery were indicated for 6 month old rats and to a lesser extent for 3 month old rats whereas no such effect was observed for older rats. Alterations in fatigue recovery were accompanied by evidence of substantial type IIb to IIx fiber type shifting. These results highlight the exceptional adaptive capacity for strength at a young age, the inclination for adaptation in fatigue recovery at early adulthood, and diminished adaptation for muscle performance in general beginning at late adulthood. Such findings motivate careful investigation to determine appropriate SSC exposures at all stages of life.

  20. Altered expression of genes regulating skeletal muscle mass in the portacaval anastomosis rat.

    PubMed

    Dasarathy, Srinivasan; Muc, Sean; Hisamuddin, Kola; Edmison, John M; Dodig, Milan; McCullough, Arthur J; Kalhan, Satish C

    2007-04-01

    We examined the temporal relationship between portacaval anastomosis (PCA), weight gain, changes in skeletal muscle mass and molecular markers of protein synthesis, protein breakdown, and satellite cell proliferation and differentiation. Male Sprague-Dawley rats with end to side PCA (n=24) were compared with sham-operated pair-fed rats (n=24). Whole body weight, lean body mass, and forelimb grip strength were determined at weekly intervals. The skeletal muscle expression of the ubiquitin proteasome system, myostatin, its receptor (the activin 2B receptor) and its signal, cyclin-dependent kinase inhibitor (CDKI) p21, insulin-like growth factor (IGF)-I and its receptor (IGF-I receptor-alpha), and markers of satellite cell proliferation and differentiation were quantified. PCA rats did not gain body weight and had lower lean body mass, forelimb grip strength, and gastrocnemius muscle weight. The skeletal muscle expression of the mRNA of ubiquitin proteasome components was higher in PCA rats in the first 2 wk followed by a lower expression in the subsequent 2 wk (P<0.01). The mRNA and protein of myostatin, activin 2B receptor, and CDKI p21 were higher, whereas IGF-I and its receptor as well as markers of satellite cell function (proliferating nuclear cell antigen, myoD, myf5, and myogenin) were lower at weeks 3 and 4 following PCA (P < 0.05). We conclude that PCA resulted in uninhibited proteolysis in the initial 2 wk. This was followed by an adaptive response in the later 2 wk consisting of an increased expression of myostatin that may have contributed to reduced muscle protein synthesis, impaired satellite cell function, and lower skeletal muscle mass.

  1. Colchicine protects rat skeletal muscle from ischemia/reperfusion injury by suppressing oxidative stress and inflammation

    PubMed Central

    Wang, Liangrong; Shan, Yuanlu; Chen, Lei; Lin, Bi; Xiong, Xiangqing; Lin, Lina; Jin, Lida

    2016-01-01

    Objective(s): Neutrophils play an important role in ischemia/reperfusion (IR) induced skeletal muscle injury. Microtubules are required for neutrophil activation in response to various stimuli. This study aimed to investigate the effects of colchicine, a microtubule-disrupting agent, on skeletal muscle IR injury in a rat hindlimb ischemia model. Materials and Methods: Twenty-one Sprague-Dawley rats were randomly allocated into three groups IR group, colchicine treated-IR (CO) group and sham operation (SM) group. Rats of both the IR and CO groups were subjected to 3 hr of ischemia by clamping the right femoral artery followed by 2 hr of reperfusion. Colchicine (1 mg/kg) was administrated intraperitoneally prior to hindlimb ischemia in the CO group. After 2 hr of reperfusion, we measured superoxide dismutase (SOD) and myeloperoxidase (MPO) activities, and malondialdehyde (MDA), tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels in the muscle samples. Plasma creatinine kinase (CK) and lactate dehydrogenase (LDH) levels were measured. We also evaluated the histological damage score and wet/dry weight (W/D) ratio. Results: The histological damage score, W/D ratio, MPO activity, MDA, TNF-α and IL-1β levels in muscle tissues were significantly increased, SOD activity was decreased, and plasma CK and LDH levels were remarkably elevated in both the IR and CO groups compared to the SM group (P<0.05). Colchicine treatment significantly reduced muscle damage and edema, oxidative stress and levels of the inflammatory parameters in the CO group compared to the IR group (P<0.05). Conclusion: Colchicine attenuates IR-induced skeletal muscle injury in rats. PMID:27482349

  2. Acute resistance exercise reduces increased gene expression in muscle atrophy of ovariectomised arthritic rats

    PubMed Central

    Furlanetto, Roberto; de Paula Souza, Aletéia; de Oliveira, Anselmo Alves; Nunes, Paulo Ricardo Prado; Michelin, Márcia Antoniazi; Chica, Javier Emilio Lazo; Murta, Eddie Fernando Candido

    2017-01-01

    Objective We studied the effect of resistance exercise (RE) on mRNA levels of atrogin-1, MuRF-1, and myostatin in the gastrocnemius muscle of arthritic rats after loss of ovarian function (LOF). Material and methods Thirty female Wistar rats (nine weeks old, 195.3 ±17.4 grams) were randomly allocated into five groups: control group (CT-Sham; n = 6); group with rheumatoid arthritis (RA; n = 6); group with rheumatoid arthritis subjected to RE (RAEX; n = 6); ovariectomy group with rheumatoid arthritis (RAOV; n = 6); and an ovariectomy group with rheumatoid arthritis subjected to RE (RAOVEX; n = 6). After 15 days of intra-articular injections with Met-BSA the animals were subjected to RE and six hours after workout were euthanised. Results The rheumatoid arthritis provoked reduction in the cross-sectional area (CSA) of muscle fibres, but the CSA was lower in the RAOV when compared to the RA groups. Skeletal muscle atrogin-1 mRNA level was increased in arthritic rats (RA and RAOV), but the atrogin-1 level was higher in RAOV group when compared to other arthritic groups. The Muscle MuRF-1 mRNA level was also increased in the RAOV group. The increased atrogin-1 and MuRF-1 mRNA levels were lower in the RAOVEX group than in the RAOV group. The myostatin mRNA level was similar in all groups, except for the RAOVEX group, in which it was lower than the other groups. Conclusions LOF results in increased loss of skeletal muscle-related ubiquitin ligases (atrogin-1 and MuRF-1). However, the RE reduces the atrogin-1, MuRF-1, and myostatin mRNA levels in muscle of arthritic rats affected by LOF. PMID:28250722

  3. Changes in nitric oxide and free radical levels in rat gastrocnemius muscle during contraction and fatigue.

    PubMed

    Ibrahim, Mariam Y; Ashour, Osama M

    2011-12-01

    1. The ratio of nitric oxide (NO) to free radicals is critical during skeletal muscle contraction. Changes in this ratio have been suggested to play a role in muscle fatigue. 2. The aim of the present study was to investigate the changes in NO and free radicals during tetanic and subtetanic contraction and fatigue in the gastrocnemius muscle of adult male Wistar rats. 3. Rats were subjected to either low- or high-frequency stimulation (10 and 100 Hz, respectively) of the right gastrocnemius muscle. Both groups were further subdivided into untreated (0.9% NaCl solution), N(G) -nitro-L-arginine methyl ester (L-NAME)-treated and reduced glutathione (GSH)-treated groups. Rats were administered their treatments intraperitoneally 30 min prior to electrical stimulation. 4. Levels of both NO and lipid peroxides increased significantly during peak force contraction for either type of contractions, with a more significant response during subtetanic contraction. Treatment with L-NAME significantly reduced the maximal force and this effect was more marked in the low frequency-stimulated group. Although peroxides levels were reduced by GSH, it had no significant effect on force production. In L-NAME-treated rats, the onset of 50% fatigue was accelerated with a significant increase in peroxides levels, whereas the opposite effects were observed after GSH treatment. 5. Current results reflect the importance of endogenous NO, as an anti-oxidant, in aiding muscle performance by overcoming oxidative stress during fatigue. They provide a possible explanation as to why patients with myopathies like Duchenne muscular dystrophy, in which dystrophin is lacking suffer from muscle weakness and fatigue easily.

  4. Immunohistochemical and functional studies on calcium-sensing receptors in rat uterine smooth muscle.

    PubMed

    Pistilli, Marc J; Petrik, James J; Holloway, Alison C; Crankshaw, Denis J

    2012-01-01

    1. Activation of calcium-sensing receptors (CaS) leads to relaxation of vascular smooth muscle. However, the role of CaS in uterine smooth muscle is unknown. Therefore the aim of the present study was to investigate the expression and function of CaS in the uterus. 2. The expression of CaS in the oestrogen-dominated rat uterus was investigated using immunohistochemistry. The effects of putative CaS ligands on oxytocin-induced contractions of longitudinally orientated uterine strips from oestrogen-dominated rats were determined at reduced extracellular Ca²⁺ concentrations using conventional organ bath techniques. 3. Immunohistochemical evidence showed the presence of CaS in the endometrium and smooth muscle layers of the rat uterus. Oxytocin-induced contractions were inhibited by cations (Gd³⁺ > Ca²⁺ = Mg²⁺), polyamines (spermine > spermidine) and the positive allosteric modulators cinacalcet and calindol. However (R)- and (S)-cinacalcet were equipotent, indicating a lack of stereoselectivity, and the negative allosteric modulator calhex-231 also caused dose-dependent relaxation. In addition, although intermediate-conductance calcium-activated potassium channels and cytochrome P450-dependent signal transduction have been implicated in CaS-induced relaxation of vascular smooth muscle, neither Tram-34 nor miconazole (1 μmol/L), which block these pathways, respectively, had any effect on the ability of cinacalcet to inhibit oxytocin-induced contractions. 4. Calcium-sensing receptors are expressed in smooth muscle layers of the rat uterus and their ligands produce potent relaxation of longitudinally orientated uterine strips. However, the pharmacological profile of inhibition of contractility by CaS ligands is not consistent with a role for CaS in the regulation of uterine contractility in the rat.

  5. Development of a behavioral assessment of craniofacial muscle pain in lightly anesthetized rats.

    PubMed

    Ro, Jin Y; Capra, Norman; Masri, Radi

    2003-07-01

    In this study, a new behavioral assessment of craniofacial muscle pain in the lightly anesthetized rat is described. Intramuscular injections with algesic agents in lightly anesthetized rats evoked a characteristic ipsilateral hindpaw shaking behavior for several minutes similar to previously described orofacial pain-induced grooming behavior in awake rats (Neurosci Lett 103 (1989) 349, Pain 62 (1995) 295). Eighty-two male Sprague-Dawley rats were used in a series of experiments to study whether this behavior could serve as a valid measure of craniofacial muscle pain. First, we demonstrated that different algesic chemicals, mustard oil (20%), formalin (3%) or hypertonic saline (5%) injected in the mid-region of the masseter muscle effectively elicited the hindpaw shaking behavior. The behavior was only minimally evoked with vehicle injection. Repeated administrations of hypertonic saline, a short duration non-sensitizing algogen, demonstrated reproducibility of the assay. Second, we showed that the peak and overall magnitude of the shaking behavior evoked by injections with different concentrations of mustard oil (1 and 5%) changed in a concentration dependent manner. Finally, we showed that systemic administration of morphine sulfate (3 and 0.3 mg/kg, i.p.) dose dependently attenuated mustard oil induced hindpaw-shaking behavior. Lidocaine injected locally 5 min prior to mustard oil injection also significantly decreased the hindpaw shaking behavior. Based on these results we concluded that ipsilateral hindpaw shaking in lightly anesthetized rats is a stereotypical behavior evoked by noxious muscle stimulation and can be used as a reliable behavioral measure to assess craniofacial muscle pain.

  6. Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

    SciTech Connect

    Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao; Martyn, J.A. Jeevendra

    2013-02-01

    Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [{sup 3}H]glucose and 2-deoxy[{sup 14}C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats.

  7. Changes in contractile activation characteristics of rat fast and slow skeletal muscle fibres during regeneration

    PubMed Central

    Gregorevic, Paul; Plant, David R; Stupka, Nicole; Lynch, Gordon S

    2004-01-01

    Damaged skeletal muscle fibres are replaced with new contractile units via muscle regeneration. Regenerating muscle fibres synthesize functionally distinct isoforms of contractile and regulatory proteins but little is known of their functional properties during the regeneration process. An advantage of utilizing single muscle fibre preparations is that assessment of their function is based on the overall characteristics of the contractile apparatus and regulatory system and as such, these preparations are sensitive in revealing not only coarse, but also subtle functional differences between muscle fibres. We examined the Ca2+- and Sr2+-activated contractile characteristics of permeabilized fibres from rat fast-twitch (extensor digitorum longus) and slow-twitch (soleus) muscles at 7, 14 and 21 days following myotoxic injury, to test the hypothesis that fibres from regenerating fast and slow muscles have different functional characteristics to fibres from uninjured muscles. Regenerating muscle fibres had ∼10% of the maximal force producing capacity (Po) of control (uninjured) fibres, and an altered sensitivity to Ca2+ and Sr2+ at 7 days post-injury. Increased force production and a shift in Ca2+ sensitivity consistent with fibre maturation were observed during regeneration such that Po was restored to 36–45% of that in control fibres by 21 days, and sensitivity to Ca2+ and Sr2+ was similar to that of control (uninjured) fibres. The findings support the hypothesis that regenerating muscle fibres have different contractile activation characteristics compared with mature fibres, and that they adopt properties of mature fast- or slow-twitch muscle fibres in a progressive manner as the regeneration process is completed. PMID:15181161

  8. [Energy reactions in the skeletal muscles of rats after a flight on the Kosmos-1129 biosatellite].

    PubMed

    Mailian, E S; Buravkova, L B; Kokoreva, L V

    1983-01-01

    The polarographic analysis of biological oxidation in rat skeletal muscles after the 18.5-day flight revealed changes specific for the flight animals: oxidative phosphorylation uncoupling, distinct inertness of energy accumulation 10 hrs after recovery. Tissue respiration inhibition occurred in both flight and synchronous rats suggesting the effect of other than weightlessness factors. In the flight animals the parameters of energy metabolism returned to the prelaunch level within a longer (29 days) time than in the synchronous rats (6 days). Muscles of different function (predominance of fast or slow fibers) showed similar responses of energy metabolism to weightlessness, i. e. inhibition of the intensity and decrease of the energy efficiency of oxidative processes.

  9. Dependence of normal development of skeletal muscle in neonatal rats on load bearing

    NASA Technical Reports Server (NTRS)

    Ohira, Y.; Tanaka, T.; Yoshinaga, T.; Kawano, F.; Nomura, T.; Nonaka, I.; Allen, D. L.; Roy, R. R.; Edgerton, V. R.

    2000-01-01

    Antigravity function plays an important role in determining the morphological and physiological properties of the neuromuscular system. Inhibition of the normal development of the neuromuscular system is induced by hindlimb unloading during the neonatal period in rats. However, the role of gravitational loading on the development of skeletal muscle in rats is not well understood. It could be hypothesized that during the early postnatal period, i.e. when minimal weight-supporting activity occurs, the activity imposed by gravity would be of little consequence in directing the normal development of the skeletal musculature. We have addressed this issue by limiting the amount of postnatal weight-support activity of the hindlimbs of rats during the lactation period. We have focused on the development of three characteristics of the muscle fibers, i.e. size, myonuclear number and myosin heavy chain expression.

  10. Lower oxidative DNA damage despite greater ROS production in muscles from rats selectively bred for high running capacity.

    PubMed

    Tweedie, Constance; Romestaing, Caroline; Burelle, Yan; Safdar, Adeel; Tarnopolsky, Mark A; Seadon, Scott; Britton, Steven L; Koch, Lauren G; Hepple, Russell T

    2011-03-01

    Artificial selection in rat has yielded high-capacity runners (HCR) and low-capacity runners (LCR) that differ in intrinsic (untrained) aerobic exercise ability and metabolic disease risk. To gain insight into how oxygen metabolism may have been affected by selection, we compared mitochondrial function, oxidative DNA damage (8-dihydroxy-guanosine; 8dOHG), and antioxidant enzyme activities in soleus muscle (Sol) and gastrocnemius muscle (Gas) of adult and aged LCR vs. HCR rats. In Sol of adult HCR rats, maximal ADP-stimulated respiration was 37% greater, whereas in Gas of adult HCR rats, there was a 23% greater complex IV-driven respiratory capacity and 54% greater leak as a fraction of electron transport capacity (suggesting looser mitochondrial coupling) vs. LCR rats. H(2)O(2) emission per gram of muscle was 24-26% greater for both muscles in adult HCR rats vs. LCR, although H(2)O(2) emission in Gas was 17% lower in HCR, after normalizing for citrate synthase activity (marker of mitochondrial content). Despite greater H(2)O(2) emission, 8dOHG levels were 62-78% lower in HCR rats due to 62-96% higher superoxide dismutase activity in both muscles and 47% higher catalase activity in Sol muscle in adult HCR rats, with no evidence for higher 8 oxoguanine glycosylase (OGG1; DNA repair enzyme) protein expression. We conclude that genetic segregation for high running capacity has generated a molecular network of cellular adaptations, facilitating a superior response to oxidative stress.

  11. Effects of aging on vasoconstrictor and mechanical properties of rat skeletal muscle arterioles

    NASA Technical Reports Server (NTRS)

    Muller-Delp, Judy; Spier, Scott A.; Ramsey, Michael W.; Lesniewski, Lisa A.; Papadopoulos, Anthony; Humphrey, J. D.; Delp, Michael D.

    2002-01-01

    Exercise capacity and skeletal muscle blood flow during exercise are reduced with advancing age. This reduction in blood flow capacity may be related to increased reactivity of skeletal muscle resistance vessels to vasoconstrictor stimuli. The purpose of this study was to test the hypothesis that aging results in increased vasoconstrictor responses of skeletal muscle resistance arterioles. First-order (1A) arterioles (90-220 microm) from the gastrocnemius and soleus muscles of young (4 mo) and aged (24 mo) Fischer-344 rats were isolated, cannulated, and pressurized via hydrostatic reservoirs. Vasoconstriction in response to increases in norepinephrine (NE; 1 x 10(-9)-1 x 10(-4) M) and KCl (20-100 mM) concentrations and increases in intraluminal pressure (10-130 cmH(2)O) were evaluated in the absence of flow. Responses to NE and KCl were similar in both soleus and gastrocnemius muscle arterioles from young and aged rats. In contrast, active myogenic responses to changes in intraluminal pressure were diminished in soleus and gastrocnemius arterioles from aged rats. To assess whether alterations in the mechanical properties of resistance arterioles underlie altered myogenic responsiveness, passive diameter responses to pressure and mechanical stiffness were evaluated. There was no effect of age on the structural behavior (passive pressure-diameter relationship) or stiffness of arterioles from either the soleus or gastrocnemius muscles. These results suggest that aging does not result in a nonspecific decrease in vasoconstrictor responsiveness of skeletal muscle arterioles. Rather, aging-induced adaptations of vasoreactivity of resistance arterioles appear to be limited to mechanisms that are uniquely involved in the signaling of the myogenic response.

  12. Effects of light-emitting diode (LED) therapy on skeletal muscle ischemia reperfusion in rats.

    PubMed

    Takhtfooladi, Mohammad Ashrafzadeh; Shahzamani, Mehran; Takhtfooladi, Hamed Ashrafzadeh; Moayer, Fariborz; Allahverdi, Amin

    2015-01-01

    Low-level laser therapy has been shown to decrease ischemia-reperfusion injuries in the skeletal muscle by induction of synthesis of antioxidants and other cytoprotective proteins. Recently, the light-emitting diode (LED) has been used instead of laser for the treatment of various diseases because of its low operational cost compared to the use of a laser. The objective of this work was to analyze the effects of LED therapy at 904 nm on skeletal muscle ischemia-reperfusion injury in rats. Thirty healthy male Wistar rats were allocated into three groups of ten rats each as follows: normal (N), ischemia-reperfusion (IR), and ischemia-reperfusion + LED (IR + LED) therapy. Ischemia was induced by right femoral artery clipping for 2 h followed by 2 h of reperfusion. The IR + LED group received LED irradiation on the right gastrocnemius muscle (4 J/cm(2)) immediately and 1 h following blood supply occlusion for 10 min. At the end of trial, the animals were euthanized and the right gastrocnemius muscles were submitted to histological and histochemical analysis. The extent of muscle damage in the IR + LED group was significantly lower than that in the IR group (P < 0.05). In comparison with other groups, tissue malondialdehyde (MDA) levels in the IR group were significantly increased (P < 0.05). The muscle tissue glutathione (GSH), superoxide dismutases (SOD), and catalase (CAT) levels in the IR group were significantly lower than those in the subjects in other groups. From the histological and histochemical perspective, the LED therapy has alleviated the metabolic injuries in the skeletal muscle ischemia reperfusion in this experimental model.

  13. The role of TRPA1 in muscle pain and mechanical hypersensitivity under inflammatory conditions in rats.

    PubMed

    Asgar, J; Zhang, Y; Saloman, J L; Wang, S; Chung, M-K; Ro, J Y

    2015-12-03

    Transient receptor potential cation channel, subfamily A, member 1 (TRPA1) is expressed in muscle afferents and direct activation of these receptors induces acute mechanical hypersensitivity. However, the functional role of TRPA1 under pathological muscle pain conditions and mechanisms by which TRPA1 mediate muscle pain and hyperalgesia are not clearly understood. Two rodent behavioral models validated to assess craniofacial muscle pain conditions were used to study ATP- and N-Methyl-D-aspartate (NMDA)-induced acute mechanical hypersensitivity and complete Freund's adjuvant (CFA)-induced persistent mechanical hypersensitivity. The rat grimace scale (RGS) was utilized to assess inflammation-induced spontaneous muscle pain. Behavioral pharmacology experiments were performed to assess the effects of AP18, a selective TRPA1 antagonist under these conditions. TRPA1 expression levels in trigeminal ganglia (TG) were examined before and after CFA treatment in the rat masseter muscle. Pre-treatment of the muscle with AP18 dose-dependently blocked the development of acute mechanical hypersensitivity induced by NMDA and α,β-methylene adenosine triphosphate (αβmeATP), a specific agonist for NMDA and P2X3 receptor, respectively. CFA-induced mechanical hypersensitivity and spontaneous muscle pain responses were significantly reversed by post-treatment of the muscle with AP18 when CFA effects were most prominent. CFA-induced myositis was accompanied by significant up-regulation of TRPA1 expression in TG. Our findings showed that TRPA1 in muscle afferents plays an important role in the development of acute mechanical hypersensitivity and in the maintenance of persistent muscle pain and hypersensitivity. Our data suggested that TRPA1 may serve as a downstream target of pro-nociceptive ion channels, such as P2X3 and NMDA receptors in masseter afferents, and that increased TRPA1 expression under inflammatory conditions may contribute to the maintenance of persistent muscle pain

  14. Dichloroacetate inhibits glycolysis and augments insulin-stimulated glycogen synthesis in rat muscle.

    PubMed Central

    Clark, A S; Mitch, W E; Goodman, M N; Fagan, J M; Goheer, M A; Curnow, R T

    1987-01-01

    The decrease in plasma lactate during dichloroacetate (DCA) treatment is attributed to stimulation of lactate oxidation. To determine whether DCA also inhibits lactate production, we measured glucose metabolism in muscles of fed and fasted rats incubated with DCA and insulin. DCA increased glucose-6-phosphate, an allosteric modifier of glycogen synthase, approximately 50% and increased muscle glycogen synthesis and glycogen content greater than 25%. Lactate release fell; inhibition of glycolysis accounted for greater than 80% of the decrease. This was associated with a decrease in intracellular AMP, but no change in citrate or ATP. When lactate oxidation was increased by raising extracellular lactate, glycolysis decreased (r = - 0.91), suggesting that lactate oxidation regulates glycolysis. When muscle lactate production was greatly stimulated by thermal injury, DCA increased glycogen synthesis, normalized glycogen content, and inhibited glycolysis, thereby reducing lactate release. The major effect of DCA on lactate metabolism in muscle is to inhibit glycolysis. PMID:3543056

  15. Role of glucocorticoids in the response of rat leg muscles to reduced activity

    NASA Technical Reports Server (NTRS)

    Jaspers, Stephen R.; Tischler, Marc E.

    1986-01-01

    Adrenalectomy did not prevent atrophy of rat soleus muscle during 6 days of tail cast suspension. Cortisol treatment enhanced the atrophy and caused atrophy of the weight-bearing soleus and both extensor digitorum longus (EDL) muscles. Unloading led to increased sarcoplasmic protein concentration in the soleus but cortisol administration increased the myhofibrillar (+stromal) protein concentration in both muscles. Suspension of hindlimbs of adrenalectomized animals led to faster protein degradation, slower sarcoplasmic protein degradation, and faster myofibrillar protein synthesis in the isolated soleus, whereas with cortisol-treated animals, the difference in synthesis of myofibrillar proteins was enhanced and that of sarcoplasmic proteins was abolished. Both soleus and EDL of suspended, cortisol-treated animals showed faster protein degradation. It is unlikely that any elevation in circulating glucocorticoids was solely responsible for atrophy of the soleus in this model, but catabolic amounts of glucocorticoids could alter the response of muscle to unloading.

  16. [Modulation of the effects of dexamethasone in rat skeletal muscle by testosterone].

    PubMed

    Trush, V V; Soboliev, V I

    2013-01-01

    In experiments on young females white rats by means of methods of electromyography and ergography we investigated the efficiency of a testosterone-propionate for smoothing of negative effects of dexamethasone on skeletal muscle. It has been established that the chronic injection of dexamethasone causes the decreasing of amplitude of contraction of forward tibial muscle on 29.7-59.3% (after 5-25 injections) and the lengthening of the latent period of muscle's excitation on 18.5-16.5% (after 15-25 injections), whereas the complex application of testosterone and dexamethasone prevents the changing of these parameters. At the same time testosterone didn't provide the smoothing of negative influence of dexamethasone on muscle's resistance to fatigue development.

  17. Microtransplantation of acetylcholine receptors from normal or denervated rat skeletal muscles to frog oocytes

    PubMed Central

    Bernareggi, Annalisa; Reyes-Ruiz, Jorge Mauricio; Lorenzon, Paola; Ruzzier, Fabio; Miledi, Ricardo

    2011-01-01

    Cell membranes, carrying neurotransmitter receptors and ion channels, can be ‘microtransplanted’ into frog oocytes. This technique allows a direct functional characterization of the original membrane proteins, together with any associated molecules they may have, still embedded in their natural lipid environment. This approach has been previously demonstrated to be very useful to study neurotransmitter receptors and ion channels contained in cell membranes isolated from human brains. Here, we examined the possibility of using the microtransplantation method to study acetylcholine receptors from normal and denervated rat skeletal muscles. We found that the muscle membranes, carrying their fetal or adult acetylcholine receptor isoforms, could be efficiently microtransplanted to the oocyte membrane, making the oocytes become sensitive to acetylcholine. These results show that oocytes injected with skeletal muscle membranes efficiently incorporate functional acetylcholine receptors, thus making the microtransplantation approach a valuable tool to further investigate receptors and ion channels of human muscle diseases. PMID:21224230

  18. Differential effect of denervation on free radical scavenging enzymes in slow and fast muscle of rat

    NASA Technical Reports Server (NTRS)

    Asayama, K.; Dettbarn, W. D.; Burr, I. M.

    1985-01-01

    To determine the effect of denervation on the free radical scavenging systems in relation to the mitochondrial oxidative metabolism in the slow twitch soleus and fast twitch extensor digitorum longus (EDL) muscles, the sciatic nerve of the rat was crushed in the mid-thigh region and the muscle tissue levels of 5 enzymes were studied 2 and 5 weeks following crush. Radioimmunoassays were utilized for the selective measurement of cuprozinc (cytosolic) and mangano (mitochondrial) superoxide dismutases. These data represent the first systematic report of free radical scavening systems in slow and fast muscles in response to denervation. Selective modification of cuprozinc and manganosuperoxide dismutases and differential regulation of GSH-peroxidase was demonstrated in slow and fast muscle.

  19. Transcriptome analysis of trigeminal ganglia following masseter muscle inflammation in rats

    PubMed Central

    Park, Jennifer; Asgar, Jamila; Ro, Jin Y.

    2016-01-01

    Background Chronic pain in masticatory muscles is a major medical problem. Although mechanisms underlying persistent pain in masticatory muscles are not fully understood, sensitization of nociceptive primary afferents following muscle inflammation or injury contributes to muscle hyperalgesia. It is well known that craniofacial muscle injury or inflammation induces regulation of multiple genes in trigeminal ganglia, which is associated with muscle hyperalgesia. However, overall transcriptional profiles within trigeminal ganglia following masseter inflammation have not yet been determined. In the present study, we performed RNA sequencing assay in rat trigeminal ganglia to identify transcriptome profiles of genes relevant to hyperalgesia following inflammation of the rat masseter muscle. Results Masseter inflammation differentially regulated >3500 genes in trigeminal ganglia. Predominant biological pathways were predicted to be related with activation of resident non-neuronal cells within trigeminal ganglia or recruitment of immune cells. To focus our analysis on the genes more relevant to nociceptors, we selected genes implicated in pain mechanisms, genes enriched in small- to medium-sized sensory neurons, and genes enriched in TRPV1-lineage nociceptors. Among the 2320 candidate genes, 622 genes showed differential expression following masseter inflammation. When the analysis was limited to these candidate genes, pathways related with G protein-coupled signaling and synaptic plasticity were predicted to be enriched. Inspection of individual gene expression changes confirmed the transcriptional changes of multiple nociceptor genes associated with masseter hyperalgesia (e.g., Trpv1, Trpa1, P2rx3, Tac1, and Bdnf) and also suggested a number of novel probable contributors (e.g., Piezo2, Tmem100, and Hdac9). Conclusion These findings should further advance our understanding of peripheral mechanisms involved in persistent craniofacial muscle pain conditions and provide a

  20. Combined isometric, concentric, and eccentric resistance exercise prevents unloading-induced muscle atrophy in rats.

    PubMed

    Adams, G R; Haddad, F; Bodell, P W; Tran, P D; Baldwin, K M

    2007-11-01

    Previously, we reported that an isometric resistance training program that was effective in stimulating muscle hypertrophy in ambulatory rats could not completely prevent muscle atrophy during unloading (Haddad F, Adams GR, Bodell PW, Baldwin KM. J Appl Physiol 100: 433-441, 2006). These results indicated that preventing muscle atrophy does not appear to be simply a function of providing an anabolic stimulus. The present study was undertaken to determine if resistance training, with increased volume (3-s contractions) and incorporating both static and dynamic components, would be effective in preventing unloading-induced muscle atrophy. Rats were exposed to 5 days of muscle unloading via tail suspension. During that time one leg received electrically stimulated resistance exercise (RE) that included an isometric, concentric, and eccentric phase. The results of this study indicate that this combined-mode RE provided an anabolic stimulus sufficient to maintain the mass and myofibril content of the trained but not the contralateral medial gastrocnemius (MG) muscle. Relative to the contralateral MG, the RE stimulus increased the amount of total RNA (indicative of translational capacity) as well as the mRNA for several anabolic/myogenic markers such as insulin-like growth factor-I, myogenin, myoferlin, and procollagen III-alpha-1 and decreased that of myostatin, a negative regulator of muscle size. The combined-mode RE protocol also increased the activity of anabolic signaling intermediates such as p70S6 kinase. These results indicate that a combination of static- and dynamic-mode RE of sufficient volume provides an effective stimulus to stimulate anabolic/myogenic mechanisms to counter the initial stages of unloading-induced muscle atrophy.

  1. Effect of mesenchymal stem cells on induced skeletal muscle chemodenervation atrophy in adult male albino rats.

    PubMed

    Shehata, Azza S; Al-Ghonemy, Nabila M; Ahmed, Samah M; Mohamed, Samar R

    2017-04-01

    The present research was conducted to evaluate the effect of bone marrow derived mesenchymal stem cells (BM-MSCs) as a potential therapeutic tool for improvement of skeletal muscle recovery after induced chemodenervation atrophy by repeated local injection of botulinum toxin-A in the right tibialis anterior muscle of adult male albino rats. Forty five adult Wistar male albino rats were classified into control and experimental groups. Experimental group was further subdivided into 3 equal subgroups; induced atrophy, BM-MSCs treated and recovery groups. Biochemical analysis of serum LDH, CK and Real-time PCR for Bcl-2, caspase 3 and caspase 9 was measured. Skeletal muscle sections were stained with H and E, Mallory trichrome, and Immunohistochemical reaction for Bax and CD34. Improvement in the skeletal muscle histological structure was noticed in BM-MSCs treated group, however, in the recovery group, some sections showed apparent transverse striations and others still affected. Immunohistochemical reaction of Bax protein showed strong positive immunoreaction in the cytoplasm of muscle fibers in the induced atrophy group. BM-MSCs treated group showed weak positive reaction while the recovery group showed moderate reaction in the cytoplasm of muscle fibers. Immunohistochemical reaction for CD34 revealed occasional positive CD34 stained cells in the induced atrophy group. In BM-MSCs treated group, multiple positive CD34 stained cells were detected. However, recovery group showed some positive CD34 stained cells at the periphery of the muscle fibers. Marked improvement in the regenerative capacity of skeletal muscles after BM-MSCs therapy. Hence, stem cell therapy provides a new hope for patients suffering from myopathies and severe injuries.

  2. ROS scavenging activity and muscle damage prevention in eccentric exercise in rats.

    PubMed

    Maruhashi, Yoshinobu; Kitaoka, Katsuhiko; Yoshiki, Yumiko; Nakamura, Ryuichi; Okano, Akira; Nakamura, Kenichi; Tsuyama, Takeshi; Shima, Yohsuke; Tomita, Katsuro

    2007-08-01

    Depending on intensity, eccentric exercise is experimentally and clinically documented to have opposing dual effects on skeletal muscle; intense eccentric exercise damages muscle, but daily low-load eccentric exercise prevents damage. To clarify the mechanisms of this dual effect, microscopic damage and oxidative stress were studied in rat quadriceps muscle. Oxidative stress was estimated from an immunostaining of advanced glycation end-products (AGE) and a measurement of muscle tissue preparations, the ability to scavenge reactive oxygen species (ROS). Intense eccentric downhill running (IEE) induced muscle damage that was, microscopically apparent 3 days later. Since AGE-positive cells and decreased ROS scavenging activity were observed earlier (on the day after IEE), cellular damage may be related to ROS production. Intense concentric uphill running (ICE) induced an immediate but transient decrease in ROS scavenging activity, which recovered within a day. Neither AGE-positive cells nor microscopic damage was observed after ICE. Since each contracting muscle fiber develops greater tension during eccentric rather than concentric exercise, the initial trigger of IEE-induced muscle damage may be damage to muscle fibers and connective tissues at the subcellular level. Daily low-load training of eccentric downhill running (LET), but not concentric uphill running, efficiently prevented muscle damage after subsequent IEE. No evident elevation of ROS scavenging activity was evident after LET. We concluded that LET prevents IEE-induced muscle damage not through elevated ROS scavenging activity, but through a suppression of initial subcellular damage that triggers subsequent ROS-producing processes, resulting in cellular delayed damage.

  3. Precocious glucocorticoid exposure reduces skeletal muscle satellite cells in the fetal rat.

    PubMed

    Gokulakrishnan, Ganga; Chang, Xiaoyan; Fleischmann, Ryan; Fiorotto, Marta L

    2017-03-01

    Perinatal skeletal muscle growth rates are a function of protein and myonuclear accretion. Precocious exposure of the fetus to glucocorticoids (GLC) in utero impairs muscle growth. Reduced muscle protein synthesis rates contribute to this response, but the consequences for myonuclear hyperplasia are unknown. To test the hypothesis that blunting of Pax7+ muscle progenitor cell proliferative activity by GLC in vivo also contributes to reduced fetal muscle growth, pregnant rats were administered dexamethasone (DEX: 1 mg/L drinking water) from embryonic day (ED) 13 to ED21. Their responses were compared to pair-fed (PF) and ad libitum-fed controls (CON). Bromodeoxyuridine (BrdU) was administered before delivery to measure myonuclear accretion. Fetal hind limb and diaphragm muscles were collected at term and analyzed for myofiber cross-sectional area (CSA), total and BrdU+ myonuclei, Pax7+ nuclei, MyoD and myogenin protein and mRNA abundance and myosin heavy chain (MyHC) isoform composition. Mean fiber CSA, myonuclei/myofiber and Pax7+ nuclei/myofiber ratios were reduced in DEX compared to those in CON and PF muscles; CSA/myonucleus, BrdU+/total myonuclei and BrdU+ myonuclei/Pax7+ nuclei were similar among groups. Myogenin abundance was reduced and MyHC-slow was increased in DEX fetuses. The data are consistent with GLC inhibition of muscle progenitor cell proliferation limiting satellite cell and myonuclear accretion. The response of PF-fed compared to CON muscles indicated that decreased food consumption by DEX dams contributed to the smaller myofiber CSA but did not affect Pax7+ nuclear accretion. Thus, the effect on satellite cell reserve and myonuclear number also contributes to the blunting of fetal muscle growth by GLC.

  4. Hsp25 and Hsp72 content in rat skeletal muscle following controlled shortening and lengthening contractions.

    PubMed

    Holwerda, Andrew M; Locke, Marius

    2014-12-01

    The cytoprotective proteins, Hsp25 and Hsp72, are increased in skeletal muscle after nondamaging, shortening contractions, but the temporal pattern of expression and stimulatory mechanisms remain unclear. Thus, we sought to define the in vivo temporal patterns of expression for Hsp25 and Hsp72 after 2 opposing contractions types. To do this, male Sprague-Dawley rats had 1 tibialis anterior (TA) muscle electrically stimulated (5 sets of 20 repetitions) while being either forcibly lengthened (LC) or shortened (SC). At 2, 8, 24, 48, 72, or 168 h after the contractions both the stimulated and the nonstimulated (contra-lateral control) TA muscles were removed and processed to examine muscle damage (hemotoxylin and eosin staining) and Hsp content (Western blot analyses). Cross-sections from TA muscles subjected to LCs showed muscle fibre damage at 8 h and thereafter. In contrast, no muscle fibre damage was observed at any time point following SCs. When normalized to contra-lateral controls, Hsp25 and Hsp72 content were significantly (P < 0.01) increased at 24 h (3.1- and 3.8-fold, respectively) and thereafter. There were no significant increases in Hsp25 or Hsp72 content at any time point following SC. These data suggest that LCs, but not SCs, result in Hsp accumulation and that the fibre/cellular damage sustained from LCs may be the stimulus for elevating Hsp content.

  5. l-Carnitine supplement reduces skeletal muscle atrophy induced by prolonged hindlimb suspension in rats.

    PubMed

    Jang, Jiwoong; Park, Jonghoon; Chang, Hyukki; Lim, Kiwon

    2016-12-01

    l-Carnitine was recently found to downregulate the ubiquitin proteasome pathway (UPP) and increase insulin-like growth factor 1 concentrations in animal models. However, the effect of l-carnitine administration on disuse muscle atrophy induced by hindlimb suspension has not yet been studied. Thus, we hypothesized that l-carnitine may have a protective effect on muscle atrophy induced by hindlimb suspension via the Akt1/mTOR and/or UPP. Male Wistar rats were assigned to 3 groups: hindlimb suspension group, hindlimb suspension with l-carnitine administration (1250 mg·kg(-1)·day(-1)) group, and pair-fed group adjusted hindlimb suspension. l-Carnitine administration for 2 weeks of hindlimb suspension alleviated the decrease in weight and fiber size in the soleus muscle. In addition, l-carnitine suppressed atrogin-1 mRNA expression, which has been reported to play a pivotal role in muscle atrophy. The present study shows that l-carnitine has a protective effect against soleus muscle atrophy caused by hindlimb suspension and decreased E3 ligase messenger RNA expression, suggesting the possibility that l-carnitine protects against muscle atrophy, at least in part, through the inhibition of the UPP. These observations suggest that l-carnitine could serve as an effective supplement in the decrease of muscle atrophy caused by weightlessness in the fields of clinical and rehabilitative research.

  6. Muscle atrophy associated with microgravity in rat: Basic data for countermeasures

    NASA Astrophysics Data System (ADS)

    Falempin, M.; Mounier, Y.

    Morphological, contractile properties and myosin heavy chain (MHC) composition of rat soleus muscles were studied after 2 weeks of unloading (HS) and after 2 weeks of HS associated with selective deafferentation (HS + DEAF) at the level L4 and L5. The same significant reductions in muscle mass and tetanic tension were found after HS and HS + DEAF. However, the transformation of the slow-twitch soleus muscle towards a faster type characterized by a decrease in twitch time parameters and an increase in fast-twitch type MHC isoforms in HS did not appear in HS + DEAF conditions. Our results also showed that a pattern similar to firing rate of motoneurones innervating slow-twitch muscles inhibited the slow to fast fiber changes observed during HS. Nevertheless, neither the loss of mass or force output in the HS muscles were prevented by electrostimulation. Immobilization in a stretched position during HS maintained the muscle wet weight, mechanical and electrophoretical characteristics close to control values. We concluded that the decrease in mechanical strains imposed on the muscle during unloading was the main factor for the development of atrophy, while the kinetic changes might be predominantly modulated by the nervous command. These basic data suggested that some experimental conditions such as electrostimulation or stretching, could participate in countermeasure programmes.

  7. The calcineurin antagonist RCAN1-4 is induced by exhaustive exercise in rat skeletal muscle.

    PubMed

    Emrani, Ramin; Rébillard, Amélie; Lefeuvre, Luz; Gratas-Delamarche, Arlette; Davies, Kelvin J A; Cillard, Josiane

    2015-10-01

    The aim of this work was to study the regulation of the calcineurin antagonist regulator of calcineurin 1 (RCAN1) in rat skeletal muscles after exhaustive physical exercise, which is a physiological modulator of oxidative stress. Three skeletal muscles, namely extensor digitorum longus (EDL), gastrocnemius, and soleus, were investigated. Exhaustive exercise increased RCAN1-4 protein levels in EDL and gastrocnemius, but not in soleus. Protein oxidation as an index of oxidative stress was increased in EDL and gastrocnemius, but remained unchanged in soleus. However, lipid peroxidation was increased in all three muscles. CuZnSOD and catalase protein levels were increased at 3 h postexercise in soleus, whereas they remained unchanged in EDL and gastrocnemius. Calcineurin enzymatic activity declined in EDL and gastrocnemius but not in soleus, and its protein expression was decreased in all three muscles. The level of PGC1-α protein remained unchanged, whereas the protein expression of the transcription factor NFATc4 was decreased in all three muscles. Adiponectin expression was increased in all three muscles. RCAN1-4 expression in EDL and gastrocnemius muscles was augmented by the oxidative stress generated from exhaustive exercise. We propose that increased RCAN1-4 expression and the signal transduction pathways it regulates represent important components of the physiological adaptation to exercise-induced oxidative stress.

  8. Increase in the amount of adenylate cyclase in rat gastrocnemius muscle after denervation

    SciTech Connect

    Hashimoto, K.; Watanabe, Y.; Uchida, S.; Yoshida, H.

    1989-01-01

    After section of the sciatic nerve, the basal adenylate cyclase (AC) activity in rat gastrocnemius muscle increased 6-7 times per membrane protein and about 2 times per whole muscle in the following 30 or 40 days. The AC activity in the muscle 30 days after denervation was increased about 4 times by folskolin. Calcitonin gene-related peptide (CGRP) also increased the adenylate cyclase activity in the denervated muscle. The binding of (/sup 3/H)-forskolin to cells isolated from gastrocnemius muscle was examined to determine the amount of AC molecules. Inhibition of (/sup 3/H)-forskolin binding by increasing amounts of unlabeled forskolin gave a sigmoid curve with a IC/sub 50/ value of 3/times/10/sup /minus/7/M. Results showed that the number of (/sup 3/H)-forskolin binding sites per cell was higher on the denervated side than on the control side, like the basal AC activity. The IC/sub 50/ values for inhibition by unlabeled forskolin of binding of (/sup 3/H)-forskolin were similar to muscles on the control and denervated sides. These results suggest that an increase in the AC activity induced by denervation was due to an increase in the numbers of AC molecules in the muscle.

  9. Short bouts of stretching increase myo-D, myostatin and atrogin-1 in rat soleus muscle.

    PubMed

    Peviani, Sabrina Messa; Gomes, Anna Raquel Silveira; Moreira, Roberta Fátima Carreira; Moriscot, Anselmo Sigari; Salvini, Tania Fátima

    2007-03-01

    Stretching is widely used in rehabilitation and sports activities to improve joint range-of-motion and flexibility in humans, but the effect of stretching on the gene expression of skeletal muscle is poorly understood. We evaluated the effect of short bouts of passive stretching of rat soleus muscle on myo-D, myostatin, and atrogin-1 gene expressions. Six groups of animals were submitted to a single session of stretching (10 stretches of 1 minute with 30 seconds of rest between them, performed manually) and were evaluated immediately (I), and 8, 24, 48, 72, and 168 hours after the session. To evaluate the effect of repetitive sessions of stretching on the soleus muscle over 1 week, three groups of animals received a single session per day of stretching and the muscle was evaluated immediately after 2, 3, and 7 sessions. The mRNA levels of myo-D, myostatin, and atrogin-1 were determined by real-time polymerase chain reaction. A single session of stretching increased the mRNA levels of myo-D (after 24 h), myostatin (I, and 168 h later), and atrogin-1 (after 48 h). Repeated daily session of stretching over 1 week increased myostatin (after 7 sessions) and atrogin-1 expression (after 2, 3, and 7 sessions). Thus, short bouts of passive stretching are able to increase the gene expression of factors associated with muscle growth (myo-D), negative regulation of muscle mass (myostatin), and atrophy (atrogin-1), indicating muscle remodeling through different pathways.

  10. Impairment of electron transfer chain induced by acute carnosine administration in skeletal muscle of young rats.

    PubMed

    Macarini, José Roberto; Maravai, Soliany Grassi; Cararo, José Henrique; Dimer, Nádia Webber; Gonçalves, Cinara Ludvig; Kist, Luiza Wilges; Bogo, Mauricio Reis; Schuck, Patrícia Fernanda; Streck, Emilio Luiz; Ferreira, Gustavo Costa

    2014-01-01

    Serum carnosinase deficiency is an inherited disorder that leads to an accumulation of carnosine in the brain tissue, cerebrospinal fluid, skeletal muscle, and other tissues of affected patients. Considering that high levels of carnosine are associated with neurological dysfunction and that the pathophysiological mechanisms involved in serum carnosinase deficiency remain poorly understood, we investigated the in vivo effects of carnosine on bioenergetics parameters, namely, respiratory chain complexes (I-III, II, and II-III), malate dehydrogenase, succinate dehydrogenase, and creatine kinase activities and the expression of mitochondrial-specific transcription factors (NRF-1, PGC-1α , and TFAM) in skeletal muscle of young Wistar rats. We observed a significant decrease of complexes I-III and II activities in animals receiving carnosine acutely, as compared to control group. However, no significant alterations in respiratory chain complexes, citric acid cycle enzymes, and creatine kinase activities were found between rats receiving carnosine chronically and control group animals. As compared to control group, mRNA levels of NRF-1, PGC-1α , and TFAM were unchanged. The present findings indicate that electron transfer through the respiratory chain is impaired in skeletal muscle of rats receiving carnosine acutely. In case these findings are confirmed by further studies and ATP depletion is also observed, impairment of bioenergetics could be considered a putative mechanism responsible for the muscle damage observed in serum carnosinase-deficient patients.

  11. Impairment of Electron Transfer Chain Induced by Acute Carnosine Administration in Skeletal Muscle of Young Rats

    PubMed Central

    Macarini, José Roberto; Maravai, Soliany Grassi; Cararo, José Henrique; Dimer, Nádia Webber; Gonçalves, Cinara Ludvig; Kist, Luiza Wilges; Bogo, Mauricio Reis; Schuck, Patrícia Fernanda; Streck, Emilio Luiz; Ferreira, Gustavo Costa

    2014-01-01

    Serum carnosinase deficiency is an inherited disorder that leads to an accumulation of carnosine in the brain tissue, cerebrospinal fluid, skeletal muscle, and other tissues of affected patients. Considering that high levels of carnosine are associated with neurological dysfunction and that the pathophysiological mechanisms involved in serum carnosinase deficiency remain poorly understood, we investigated the in vivo effects of carnosine on bioenergetics parameters, namely, respiratory chain complexes (I–III, II, and II-III), malate dehydrogenase, succinate dehydrogenase, and creatine kinase activities and the expression of mitochondrial-specific transcription factors (NRF-1, PGC-1α, and TFAM) in skeletal muscle of young Wistar rats. We observed a significant decrease of complexes I–III and II activities in animals receiving carnosine acutely, as compared to control group. However, no significant alterations in respiratory chain complexes, citric acid cycle enzymes, and creatine kinase activities were found between rats receiving carnosine chronically and control group animals. As compared to control group, mRNA levels of NRF-1, PGC-1α, and TFAM were unchanged. The present findings indicate that electron transfer through the respiratory chain is impaired in skeletal muscle of rats receiving carnosine acutely. In case these findings are confirmed by further studies and ATP depletion is also observed, impairment of bioenergetics could be considered a putative mechanism responsible for the muscle damage observed in serum carnosinase-deficient patients. PMID:24877122

  12. [Response properties of the jaw-closing muscle spindle during decreased occlusal vertical dimension in rats].

    PubMed

    Fujita, Koichi

    2008-03-01

    The masseter-muscle spindle is regarded as being highly adaptable to increases in the occlusal vertical dimension (iOVD), it is hypothesized that spindle function would adapt to a decrease in occlusal vertical dimension (dOVD) as well. Seventy-five 5-week-old female Wistar rats were divided into Control (n = 25) and Experimental (n = 50) groups; those in the Experimental group received a 2.0-mm composite resin build-up to the maxillary molars. The Experimental group was divided into the resin-removal group (n = 25, build-up resin was removed) and the non resin-removal group (n = 25) 8 weeks later; i. e., when the animals were 13 weeks old. Electrophysiological recordings were obtained from masseter-muscle spindle afferents in 13, 14, 15, 19, 21-week-old rats (n = 5 rats each) under general anesthesia Masseter-muscle spindle sensitivity was significantly lower in the resin-removal group 1 week after resin-removal and for the rest of the observation period. The present results indicate that masseter-muscle spindles may not completely adapt to dOVD and may affect jaw function.

  13. Aging-induced alterations in female rat colon smooth muscle: the protective effects of hormonal therapy.

    PubMed

    Pascua, P; Camello-Almaraz, C; Pozo, M J; Martin-Cano, F E; Vara, E; Fernández-Tresguerres, J A; Camello, P J

    2012-06-01

    Aging is associated to oxidative damage and alterations in inflammatory and apoptotic pathways. Aging impairs secretion of several hormones, including melatonin and estrogens. However, the mechanisms involved in aging of smooth muscle are poorly known. We have studied the changes induced by aging in the colonic smooth muscle layer of female rats and the protective effect of hormonal therapy. We used young, aged, and ovariectomized aged female rats. Two groups of ovariectomized rats (22 months old) were treated either with melatonin or with estrogen for 10 weeks before sacrifice. Aging induced oxidative imbalance, evidenced by H(2)O(2) accumulation, lipid peroxidation, and decreased catalase activity. The oxidative damage was enhanced by ovariectomy. In addition, aged colonic muscle showed enhanced expression of the pro-inflammatory enzyme cyclooxygenase 2. Expression of the activated forms of caspases 3 and 9 was also enhanced in aged colon. Melatonin and estrogen treatment prevented the oxidative damage and the activation of caspases. In conclusion, aging of colonic smooth muscle induces oxidative imbalance and activation of apoptotic and pro-inflammatory pathways. Hormonal therapy has beneficial effects on the oxidative and apoptotic changes associated to aging in this model.

  14. Adrenodemedullation activates the Ca(2+)-dependent proteolysis in soleus muscles from rats exposed to cold.

    PubMed

    Manfredi, L H; Lustrino, D; Machado, J; Silveira, W A; Zanon, N M; Navegantes, L C; Kettelhut, I C

    2017-02-01

    Previous studies have shown that catecholamines in vivo and in vitro inhibit the activity of Ca(2+)-dependent proteolysis in skeletal muscles under basal conditions. In the present study we sought to investigate the role of catecholamines in regulating the Ca(2+)-dependent proteolysis in soleus and extensor digitorum longus (EDL) muscles from rats acutely exposed to cold. Overall proteolysis, the activity of proteolytic systems, protein levels and gene expression of different components of the calpain system were investigated in rats submitted to adrenodemedullation (ADMX) and exposed to cold for 24 h. ADMX drastically reduced plasma epinephrine and promoted an additional increase in the overall proteolysis, which was already increased by cold exposure. The rise in the rate of protein degradation in soleus muscles from adrenodemedullated cold-exposed rats was caused by the high activity of the Ca(2+)-dependent proteolysis, which was associated with the generation of a 145-kDa cleaved α-fodrin fragment, a typical calpain substrate, and lower protein levels and mRNA expression of calpastatin, the endogenous calpain inhibitor. Unlike that observed for soleus muscles, the cold-induced muscle proteolysis in EDL was not affected by ADMX. In isolated soleus muscle, clenbuterol, a selective β2-adrenoceptor agonist, reduced the basal Ca(2+)-dependent proteolysis and completely abolished the activation of this pathway by the cholinergic agonist carbachol. These data suggest that catecholamines released from the adrenal medulla inhibit cold-induced protein breakdown in soleus, and this antiproteolytic effect on the Ca(2+)-dependent proteolytic system is apparently mediated through expression of calpastatin, which leads to suppression of calpain activation.NEW & NOTEWORTHY Although many effects of the sympathetic nervous system on muscle physiology are known, the role of catecholamines in skeletal muscle protein metabolism has been scarcely studied. We suggest that

  15. High-phosphorus diet maximizes and low-dose calcitriol attenuates skeletal muscle changes in long-term uremic rats.

    PubMed

    Acevedo, Luz M; López, Ignacio; Peralta-Ramírez, Alan; Pineda, Carmen; Chamizo, Verónica E; Rodríguez, Mariano; Aguilera-Tejero, Escolástico; Rivero, José-Luis L

    2016-05-01

    Although disorders of mineral metabolism and skeletal muscle are common in chronic kidney disease (CKD), their potential relationship remains unexplored. Elevations in plasma phosphate, parathyroid hormone, and fibroblastic growth factor 23 together with decreased calcitriol levels are common features of CKD. High-phosphate intake is a major contributor to progression of CKD. This study was primarily aimed to determine the influence of high-phosphate intake on muscle and to investigate whether calcitriol supplementation counteracts negative skeletal muscle changes associated with long-term uremia. Proportions and metabolic and morphological features of myosin-based muscle fiber types were assessed in the slow-twitch soleus and the fast-twitch tibialis cranialis muscles of uremic rats (5/6 nephrectomy, Nx) and compared with sham-operated (So) controls. Three groups of Nx rats received either a standard diet (0.6% phosphorus, Nx-Sd), or a high-phosphorus diet (0.9% phosphorus, Nx-Pho), or a high-phosphorus diet plus calcitriol (10 ng/kg 3 day/wk ip, Nx-Pho + Cal) for 12 wk. Two groups of So rats received either a standard diet or a high-phosphorus diet (So-Pho) over the same period. A multivariate analysis encompassing all fiber-type characteristics indicated that Nx-Pho + Cal rats displayed skeletal muscle phenotypes intermediate between Nx-Pho and So-Pho rats and that uremia-induced skeletal muscle changes were of greater magnitude in Nx-Pho than in Nx-Sd rats. In uremic rats, treatment with calcitriol preserved fiber-type composition, cross-sectional size, myonuclear domain size, oxidative capacity, and capillarity of muscle fibers. These data demonstrate that a high-phosphorus diet potentiates and low-dose calcitriol attenuates adverse skeletal muscle changes in long-term uremic rats.

  16. Desensitized morphological and cytokine response after stretch-shortening muscle contractions as a feature of aging in rats.

    PubMed

    Rader, Erik P; Layner, Kayla N; Triscuit, Alyssa M; Kashon, Michael L; Gu, Ja K; Ensey, James; Baker, Brent A

    2015-12-01

    Recovery from contraction-induced injury is impaired with aging. At a young age, the secondary response several days following contraction-induced injury consists of edema, inflammatory cell infiltration, and segmental muscle fiber degeneration to aid in the clearance of damaged tissue and repair. This morphological response has not been wholly established at advanced age. Our aim was to characterize muscle fiber morphology 3 and 10 days following stretch-shortening contractions (SSCs) varying in repetition number (i.e. 0, 30, 80, and 150) for young and old rats. For muscles of young rats, muscle fiber degeneration was overt at 3 days exclusively after 80 or 150 SSCs and returned significantly closer to control values by 10 days. For muscles of old rats, no such responses were observed. Transcriptional microarray analysis at 3 days demonstrated that muscles of young rats differentially expressed up to 2144 genes while muscles of old rats differentially expressed 47 genes. Bioinformatic analysis indicated that cellular movement was a major biological process over-represented with genes that were significantly altered by SSCs especially for young rats. Protein levels in muscle for various cytokines and chemokines, key inflammatory factors for cell movement, increased 3- to 50-fold following high-repetition SSCs for young rats with no change for old rats. This age-related differential response was insightful given that for control (i.e. 0 SSCs) conditions, protein levels of circulatory cytokines/chemokines were increased with age. The results demonstrate ongoing systemic low-grade inflammatory signaling and subsequent desensitization of the cytokine/chemokine and morphological response to contraction-induced injury with aging - features which accompany age-related impairment in muscle recovery.

  17. Systemic elevation of interleukin-15 in vivo promotes apoptosis in skeletal muscles of young adult and aged rats.

    PubMed

    Pistilli, Emidio E; Alway, Stephen E

    2008-08-15

    In this study, we tested the hypothesis that systemic elevation of IL-15 would attenuate apoptosis in skeletal muscles of aged rats. IL-15 was administered to young adult (n=6) and aged (n=6) rats for 14 days. Apoptosis was quantified using an ELISA assay and verified through TUNEL staining of muscle sections. As expected, apoptosis was greater in muscles from aged control rats, compared to age-matched control. Apoptosis was also greater in the muscles from young adult and aged rats treated with IL-15. These increases in apoptosis were associated with decreases in muscle mass of IL-15 treated rats. These data do not support our initial hypothesis and suggest that systemic elevation of IL-15 promotes apoptosis in skeletal muscle. The proposed anti-apoptotic property of IL-15 may be specific to cell-type and/or the degree of muscle pathology present; however, additional research is required to more clearly decipher its role in skeletal muscle.

  18. Creatine Supplementation Induces Alteration in Cross-Sectional Area in Skeletal Muscle Fibers of Wistar Rats Under Swimming Training

    PubMed Central

    Santos, Fernando Farias Dos; Moura, José A. A.; Curi, Rui; Fernandes, Luiz C.

    2002-01-01

    Creatine has been shown to increase the total muscle mass. In this study, we investigated the effect of oral creatine monohydrate supplementation on cross-sectional area of type I, IIA and IIB fibers of gastrocnemius, extensor digitorum longus - EDL and soleus muscles from male Wistar rats subjected to swimming training for 33 days. Four groups were set up: sedentary with no supplementation (CON), sedentary with creatine supplementation (3.3 mg creatine per g chow) (CR), exercised with no supplementation (EX) and exercised with supplementation (CREX). The rats performed in a special swimming pool and swam five times a week for 1 hour each day, with a extra lead weight corresponding to 15% of their body weight. At the end of 33 days, skeletal muscles of the animals were dissected and the samples got immediately frozen using liquid nitrogen. Muscle samples were allocated to slices of 10 μm by a cryostat at -20°C, which was followed by histochemical analysis in order to identify fiber types of the muscles, and morphometrical analysis to calculate the muscle fiber areas. All groups gained body weight at the end of 33 days but there was no statistical difference among them. The EX and CREX rats had a larger food intake than the sedentary groups (CON and CR), and the CREX group had a larger food intake than CR rats. The cross-sectional area of type I and IIA fibers of the soleus muscle, type IIA and IIB fibers of EDL muscle and type IIA and IIB fibers of the white portion of gastrocnemius muscle were greater in the EX and CREX groups in comparison to sedentary rats. In addition, these fibers were greater in the CREX rats than in the EX group. There was no change in the cross sectional area of type I fibers in EDL muscle among all groups studied. Our results suggest that creatine supplementation enhances the exercise related muscle fiber hypertrophy in rodents. PMID:24701129

  19. Influence of 7 days of hindlimb suspension and intermittent weight support on rat muscle mechanical properties

    NASA Technical Reports Server (NTRS)

    Pierotti, David J.; Roy, Roland R.; Flores, Vinicio; Edgerton, Reggie

    1990-01-01

    The effect of intermittent periods of weight support on a decrease in mass of the soleus (Sol) and medial gastrocnemius (MG) muscles atrophied by hindlimb suspension (HS) was investigated in rats subjected to continuous HS for seven days or an HS plus intermittent (10 min every 6 hrs of slow walking on a treadmill) weight support (HS-WS). After 7 d HS, the Sol weight relative to body weight was 21 and 9 percent lower in Hs and HS-WS, respectively, than in control rats. Maximum tetanic tension/muscle mass ratio was significantly lower in HS than in controls; the HS-WS rats had values similar to controls, whereas the maximum tetanic tension/muscle weight was significantly elevated in HS-WS compared to controls. Contraction times were 25 percent faster in the Sol and unchanged in the MG of HS rats, indicating that a low-force short-duration exercise regime results in a significant functional recovery in the 'slow' Sol, whereas the 'fast' MG is less affected.

  20. Efficacy of maslinic acid and fenbendazole on muscle larvae of Trichinella zimbabwensis in laboratory rats.

    PubMed

    Mukaratirwa, S; Gcanga, L; Kamau, J

    2016-01-01

    Trichinellosis is a zoonotic disease caused by nematode species of the genus Trichinella. Anthelmintics targeting the intestinal adults and muscle-dwelling larvae of Trichinella spp. have been tested, with limited success. This study was aimed at determining the efficacy of maslinic acid and fenbendazole on muscle larvae of Trichinella zimbabwensis in laboratory rats. Forty-two Sprague-Dawley rats, with an average weight of 270 g and 180 g for males and females respectively, were infected with T. zimbabwensis larvae. Infected rats were randomly assigned to three groups which were subjected to single treatments with each of maslinic acid, fenbendazole and a combination of both on day 25 post-infection (pi), and three groups which were subjected to double treatments with each of these drugs and a combination on days 25 and 32 pi. The untreated control group received a placebo. In single-treatment groups, the efficacy of each treatment, measured by rate of reduction in muscle larvae, was significant (P0.05). We conclude that the efficacy of maslinic acid against larval stages of T. zimbabwensis in rats was comparable to that of fenbendazole, with no side-effects observed, making maslinic acid a promising anthelmintic against larval stages of Trichinella species.

  1. The effects of isoflurane on airway smooth muscle crossbridge kinetics in Fisher and Lewis rats.

    PubMed

    Duracher, Caroline; Blanc, François-Xavier; Gueugniaud, Pierre-Yves; David, Jean Stéphane; Riou, Bruno; Lecarpentier, Yves; Coirault, Catherine

    2005-07-01

    Our aim was to determine how isoflurane modified crossbridge (CB) number and kinetics in airway smooth muscle (ASM) and to compare its effects in Fisher and Lewis rats, two strains with differences in airway responsiveness. The effects of isoflurane (2 MAC) on isotonic and isometric contractility in tracheal ASM strips were investigated after methacholine (10(-6) M)-induced contraction. CB mechanics and kinetics were analyzed using the formalism of Huxley's equations adapted to ASM. After isoflurane, maximum velocity did not differ from baseline in Lewis rats, whereas it was significantly less than baseline in Fisher rats ( approximately 25%), the most reactive strain. Isoflurane totally reversed methacholine-induced increase in active CB number in Lewis rats (2.4 +/- 0.5 versus 1.8 +/- 0.4 10(9)/mm(2) after methacholine and isoflurane, respectively) whereas reversal was only partial in Fisher rats (2.7 +/- 0.4 versus 2.1 +/- 0.3 10(9)/mm(2) after methacholine and isoflurane, respectively). Isoflurane induced a 40% increase in attachment step duration in both strains and an almost twofold increase in the CB cycle duration compared with baseline in Lewis rats. The isoflurane-induced increase in detachment step duration was less in Lewis than in Fisher rats (P < 0.05). We concluded that isoflurane modulated CB number and CB cycling rates of isolated rat ASM differently depending on the level of airway responsiveness.

  2. Effects of thyroxine on rat brown fat and muscle thermogenesis in the cold.

    PubMed

    Zaninovich, A A; Rebagliati, I; Raíces, M; Ricci, C; Hagmüller, K

    2000-05-01

    We studied whether the activation of rat brown adipose tissue (BAT) by cold exposure or by the administration of beta-3-noradrenergic agonist CGP-12177 could be prevented by the inhibition of thyroxine (T4) to triiodothyronine (T3) conversion. Hypothyroid rats were treated with replacement doses of T4, T4 plus iopanoic acid (IA) or T3. Groups of rats were placed at 4 degrees C for 24 h or kept at room temperature. Cold exposure induced a significant increase in guanosine diphosphate (GDP) binding to BAT mitochondrial proteins in T4-treated rats, an effect not abolished by IA. No significant changes were seen in T3-treated rats. In rats maintained at room temperature and injected with CGP-12177, T4 induced a significant rise in GDP binding which was not blocked by IA. T3 also induced a significant increase in binding. The study of mitochondrial oxygen consumption in muscle from cold-exposed rats showed a marked decrease in consumption in T3-treated rats as compared to values in the warm. Normal oxygen consumption was restored with 2-fold doses of T3 replacement, whereas 5-fold doses increased consumption above normal. The data suggest that in states with low or absent T3, T4 can stimulate heat production and preserve normothermia.

  3. [Nandrolone administration does not promote hypertrophy of soleus muscle in rats].

    PubMed

    Cunha, Tatiana S; Tanno, Ana Paula; Marcondes, Fernanda K; Perez, Sérgio E A; Selistre-Araújo, Heloisa S

    2006-06-01

    Anabolic androgenic steroids (AAS) are compounds formed from testosterone or one of its derivatives, which are largely used by amateur e professional athletes to improve the athletic performance. However, the scientific information about the relation between the use of AAS and muscle hypertrophy is controversial. The aim of this study was to evaluate the effects of testosterone and physical training on muscle hypertrophy. Male Wistar rats received i.m. injections of Deca-Durabolin or vehicle during 6 weeks. Trained rats were submitted to a resistance physical training, by jumping up and down in water carrying an overload. Sedentary and trained animals were anesthetized and sacrificed. Soleus muscle was removed for the quantification of total protein and DNA concentration. In the end of the treatment, body weight of trained animals treated with vehicle or AAS was lower than the body weight of respective sedentary. Total protein concentration and the ratio muscle weight/body weight of all experimental groups were not altered. Trained group treated with AAS presented lower DNA concentration than trained group treated with vehicle. The administration of nandrolone decanoate did not promote hypertrophy on soleus muscle, not even when the use of AAS was associated to resistance physical training.

  4. Prior swimming exercise favors muscle recovery in adult female rats after joint immobilization

    PubMed Central

    Petrini, Ana Claudia; Ramos, Douglas Massoni; Gomes de Oliveira, Luana; Alberto da Silva, Carlos; Pertille, Adriana

    2016-01-01

    [Purpose] To evaluate the efficacy of pre-exercise on immobilization and subsequent recovery of white gastrocnemius (WG) and soleus (SOL) muscles of female rats. [Subjects and Methods] Thirty, 8-month-old, female Wistar rats were randomly and evenly allocated to six groups: sedentary (S); immobilized sedentary (IS); immobilized/rehabilitated sedentary (IRS); trained (T); immobilized trained (IT); and immobilized/rehabilitated trained (IRT). For four months, T, IT and IRT group animals performed swimming exercise (three sessions per week, 60 minutes per session), while S, IS and IRS groups animals remained housed in cages. After this period, the left hindlimb of the animals from the IS, IRS, IT and IRT groups was immobilized for five days, with the ankle at 90°. After removal of the orthosis, animals from the IRS and IRT groups followed a rehabilitation program based on swimming (five sessions per week, 60 minutes per session) for two weeks. [Results] Immobilization significantly reduced the cross-sectional area of the white gastrocnemius muscle; no changes were observed in the soleus muscles of the trained animals. Transforming growth factor-β1 protein levels were similar among the trained groups. [Conclusion] Prior swimming prevents hypotrophy of the soleus muscle after immobilization, and protein levels reflected the adaptive capacity of the skeletal muscle. PMID:27512267

  5. Regulator of insulin receptor affinity in rat skeletal muscle sarcolemmal vesicles

    SciTech Connect

    Whitson, R.H.; Barnard, K.J.; Kaplan, S.A.; Itakura, K.

    1986-05-01

    Wheat germ agglutinin (WGA) affinity purification of detergent solubilized insulin receptors (IR) from rat skeletal muscle sarcolemmal vesicles resulted in an apparent increase in total insulin binding activity of greater than 5-fold, suggesting that an inhibitory component had been removed. This was verified when the flow-through fraction from the WGA column was dialyzed and added back to the partially purified receptor. The addition of a 100-fold dilution of the inhibitor preparation caused a 50% reduction in binding to trace amounts of /sup 125/I-insulin. Scatchard analysis revealed that the effect of the inhibitor was to decrease the affinity of the muscle IR. The inhibitor appeared to be tissue specific, inasmuch as the I/sub 50/'s for WGA-purified IR from rat fat and liver were 10 times the I/sub 50/ for muscle IR. The I/sub 50/ for insulin binding to intact IM-9 cells was 30 times the value for muscle IR. The inhibitor eluted in the void volume of Sephadex G-50 columns. Its activity was not destroyed by heating at 90/sup 0/C for 10 minutes, or by prolonged incubation with trypsin or dithiothreitol. The inhibitor described here may have a role in modulating insulin sensitivity in skeletal muscle.

  6. Effect of oxidative stress on Rho kinase II and smooth muscle contraction in rat stomach.

    PubMed

    Al-Shboul, Othman; Mustafa, Ayman

    2015-06-01

    Recent studies have shown that both Rho kinase signaling and oxidative stress are involved in the pathogenesis of a number of human diseases, such as diabetes mellitus, hypertension, and atherosclerosis. However, very little is known about the effect of oxidative stress on the gastrointestinal (GI) smooth muscle Rho kinase pathway. The aim of the current study was to investigate the effect of oxidative stress on Rho kinase II and muscle contraction in rat stomach. The peroxynitrite donor 3-morpholinosydnonimine (SIN-1), hydrogen peroxide (H2O2), and peroxynitrite were used to induce oxidative stress. Rho kinase II expression and ACh-induced activity were measured in control and oxidant-treated cells via specifically designed enzyme-linked immunosorbent assay (ELISA) and activity assay kits, respectively. Single smooth muscle cell contraction was measured via scanning micrometry in the presence or absence of the Rho kinase blocker, Y-27632 dihydrochloride. All oxidant agents significantly increased ACh-induced Rho kinase II activity without affecting its expression level. Most important, oxidative stress induced by all three agents augmented ACh-stimulated muscle cell contraction, which was significantly inhibited by Y-27632. In conclusion, oxidative stress activates Rho kinase II and enhances contraction in rat gastric muscle, suggesting an important role in GI motility disorders associated with oxidative stress.

  7. Effect of chronic ethanol ingestion and exercise training on skeletal muscle in rat.

    PubMed

    Vila, L; Ferrando, A; Voces, J; Cabral de Oliveira, C; Prieto, J G; Alvarez, A I

    2001-09-01

    The aim of this study was to investigate the interactive effects of exercise training and chronic ethanol consumption on metabolism, capillarity, and myofibrillar composition in rat limb muscles. Male Wistar rats were treated in separate groups as follows: non exercised-control; ethanol (15%) in animals' drinking water for 12 weeks; exercise training in treadmill and ethanol administration plus exercise for 12 weeks. Ethanol administration decreased capillarity and increased piruvate kinase and lactate dehydrogenase activities in white gastrocnemius; in plantaris muscle, ethanol increased citrate synthase activity and decreased cross-sectional area of type I, IIa, and IIb fibres. Exercise increased capillarity in all four limb muscles and decreased type I fibre area in plantaris. The decreased capillarity effect induced by ethanol in some muscles, was ameliorated when alcohol was combined with exercise. While alcoholic myopathy affects predominantly type IIb fibres, ethanol administration and aerobic exercise in some cases can affect type I and type IIa fibre areas. The exercise can decrease some harmful effects produced by ethanol in the muscle, including the decrease in the fibre area and capillary density.

  8. Small bowel transplantation induces adrenergic hypersensitivity in ileal longitudinal smooth muscle in rats.

    PubMed

    Ohtani, N; Balsiger, B M; Anding, W J; Duenes, J A; Sarr, M G

    2000-01-01

    Our aim was to determine the effects of small bowel transplantation on contractility of longitudinal muscle in the rat ileum. Full-thickness longitudinal muscle strips from four groups of rats (naive controls, sham-operated controls, and 1 week and 8 weeks after syngeneic orthotopic small bowel transplantation) were studied in vitro. Neither baseline contractility nor response to neural blockade (tetrodotoxin) or adrenergic/cholinergic blockade differed among the groups. Although the dose response to the cholinergic agonist bethanechol and to nitric oxide did not differ among groups, the ED50 (negative log of concentration giving half-maximal effect) for the adrenergic agonist norepinephrine was increased l week and 8 weeks after transplantation, indicating a hypersensitivity response not blocked by tetrodotoxin. Nonadrenergic, noncholinergic inhibitory responses to electrical field stimulation were of greater amplitude and occurred at lesser frequencies (>/=5 Hz) 1 week after small bowel transplantation, but returned to control values 8 weeks postoperatively. These inhibitory responses were blocked by the nitric oxide synthase inhibitor L-NMMA but not by methylene blue, a nonspecific inhibitor of guanylate cyclase. Small bowel transplantation induces a persistent adrenergic denervation hypersensitivity at the muscle and appears to upregulate, at least transiently, other inhibitory mechanisms mediated by neural release of nitric oxide. Small bowel transplantation does not alter muscle response to cholinergic pathways. These alterations in smooth muscle contractility may affect gut function early after clinical small bowel transplantation.

  9. Effect of recovery mode following hind-limb suspension on soleus muscle composition in the rat

    NASA Technical Reports Server (NTRS)

    McNulty, A. L.; Otto, A. J.; Kasper, C. E.; Thomas, D. P.

    1992-01-01

    The purpose of this study was to compare the effects of two different recovery modes from hind-limb suspension-induced hypodynamia on whole body and muscle (soleus) growth as well as soleus composition and size changes of different fiber types within this same muscle. Following 28 days of tail-suspension, rats were returned to their cages and sedentarily recovered (HS), or were exercised by running on a treadmill 5 days/wk, at progressively increasing workloads (HR) for one month. Sedentary and running control groups of animals (CS, CR) were also evaluated for comparative purposes. The exercise program, which was identical for CR and HR groups, had no effect on body wt., soleus wt., soleus muscle composition or fiber size in CR rats. Atrophied soleus muscle and reduced soleus wt./body wt. ratio (both 60% of control) had returned to control values by day 7 of recovery in both suspended groups despite the fact that whole body wt. gain was significantly reduced (p less than 0.05) in HR as compared to HS rats. Atrophied soleus Type I fiber mean cross-sectional area in both HR and HS groups demonstrated similar and significant (p less than 0.01) increases during recovery. Increases in Type IIa and IIc fiber area during this same period were significant only in the HR group. While the percentage area of muscle composed of Type I fibers increased in both hypodynamic groups during recovery, the reduction in area percentage of muscle made up of Type IIa fibers was again only significant in the HR group.(ABSTRACT TRUNCATED AT 250 WORDS).

  10. Effects of space flight on GLUT-4 content in rat plantaris muscle

    NASA Astrophysics Data System (ADS)

    Tabata, I.; Kawanaka, Kentaro; Sekiguchi, Chiharu; Nagaoka, Shunji; Ohira, Yoshinobu

    The effects of 14 days of space flight on the glucose transporter protein (GLUT-4) were studied in the plantaris muscle of growing 9-week-old, male Sprague Dawley rats. The rats were randomly separated into five groups: pre-flight vivarium ground controls (PF-VC) sacrificed approximately 2 h after launch; flight groups sacrificed either approximately 5 h (F-R0) or 9 days (F-R9) after the return from space; and synchronous ground controls (SC-R0 and SC-R9) sacrificed at the same time as the respective flight groups. The flight groups F-R0 and F-R9 were exposed to micro-gravity for 14 days in the Spacelab module located in the cargo bay of the shuttle transport system - 58 of the manned Space Shuttle for the NASA mission named ''Spacelab Life Sciences 2''. Body weight and plantaris weight of SC-R0 and F-R0 were significantly higher than those of PF-VC. Neither body weight nor plantaris muscle weight in either group had changed 9 days after the return from space. As a result, body weight and plantaris muscle weight did not differ between the flight and synchronous control groups at any of the time points investigated. The GLUT-4 content (cpm/µg membrane protein) in the plantaris muscle did not show any significant change in response to 14 days of space flight or 9 days after return. Similarly, citrate synthase activity did not change during the course of the space flight or the recovery period. These results suggest that 14 days of space flight does not affect muscle mass or GLUT-4 content of the fast-twitch plantaris muscle in the rat.

  11. Subglottal pressure, tracheal airflow, and intrinsic laryngeal muscle activity during rat ultrasound vocalization

    PubMed Central

    2011-01-01

    Vocal production requires complex planning and coordination of respiratory, laryngeal, and vocal tract movements, which are incompletely understood in most mammals. Rats produce a variety of whistles in the ultrasonic range that are of communicative relevance and of importance as a model system, but the sources of acoustic variability were mostly unknown. The goal was to identify sources of fundamental frequency variability. Subglottal pressure, tracheal airflow, and electromyographic (EMG) data from two intrinsic laryngeal muscles were measured during 22-kHz and 50-kHz call production in awake, spontaneously behaving adult male rats. During ultrasound vocalization, subglottal pressure ranged between 0.8 and 1.9 kPa. Pressure differences between call types were not significant. The relation between fundamental frequency and subglottal pressure within call types was inconsistent. Experimental manipulations of subglottal pressure had only small effects on fundamental frequency. Tracheal airflow patterns were also inconsistently associated with frequency. Pressure and flow seem to play a small role in regulation of fundamental frequency. Muscle activity, however, is precisely regulated and very sensitive to alterations, presumably because of effects on resonance properties in the vocal tract. EMG activity of cricothyroid and thyroarytenoid muscle was tonic in calls with slow or no fundamental frequency modulations, like 22-kHz and flat 50-kHz calls. Both muscles showed brief high-amplitude, alternating bursts at rates up to 150 Hz during production of frequency-modulated 50-kHz calls. A differentiated and fine regulation of intrinsic laryngeal muscles is critical for normal ultrasound vocalization. Many features of the laryngeal muscle activation pattern during ultrasound vocalization in rats are shared with other mammals. PMID:21832032

  12. Repeated bouts of fast velocity eccentric contractions induce atrophy of gastrocnemius muscle in rats.

    PubMed

    Ochi, Eisuke; Nosaka, Kazunori; Tsutaki, Arata; Kouzaki, Karina; Nakazato, Koichi

    2015-10-01

    One bout of exercise consisting of fast velocity eccentric contractions has been shown to increase muscle protein degradation in rats. The present study tested the hypothesis that muscle atrophy would be induced after four bouts of fast velocity eccentric contractions, but not after four bouts of slow velocity eccentric contractions. Male Wistar rats were randomly placed into 3 groups; fast (180°/s) velocity (180EC, n = 7), slow (30°/s) velocity eccentric exercise (30EC, n = 7), or sham-treatment group (control, n = 7). The 180EC and 30EC groups received 4 sessions of 4 sets of 5 eccentric contractions of triceps surae muscles by extending the ankle joint during evoked electrical stimulation of the muscles, and the control group had torque measures, every 2 days, and all rats were sacrificed 1 day after the fourth session. Medial and lateral gastrocnemius wet mass were 4-6 % smaller, cross-sectional area of medial gastrocnemius was 6-7% smaller, and isometric tetanic torque of triceps surae muscles was 36 % smaller (p < 0.05) for 180EC than control at 1 day after the fourth session, but no such differences were evident between 30EC and control. The expressions of atrophy-related molecules such as FoxO1, FoxO3 and myostatin were upregulated (78-229 %) only for 180EC, but an increase in phosphorylated p70s6k (227%) was found only for 30EC at 1 day after the fourth session (p < 0.05). The level of Bax, a pro-apoptotic protein, was greater (p < 0.05) for 180EC than control. These results support the hypothesis that muscles are atrophied by repeated bouts of fast but not slow velocity eccentric contractions.

  13. Electromyographic studies regarding denervation potentials in skeletal muscles at sites near and distant from the burn in rats.

    PubMed

    Sajadi, Simin; Mansoori, Korosh; Forogh, Bijan; Fatemi, Mohammad Javad; Ahadi, Tannaz; Chahardoli Razji, Mahnaz

    2016-04-01

    Changes in membrane AChRs in skeletal muscles located near or distant from burn injury similar to denervated muscles may make electrodiagnostic features indistinguishable from true neuropathic changes. The aim of this study was to examine electrodiagnostic changes of muscles at sites local and distant from the burn after thermal injuries due to neuromuscular junction dysfunction. A total of 40 adult male rats were randomly allocated to four groups. Rats in group 1 received thermal burn injury over gastrocnemius muscle of one leg and sham burn on the other leg. A 20-25% and 30-35% surface body area burn and also 30-35% surface body area sham burn were produced at distant site from gastrocnemius muscle in group 2, 3 and 4, respectively. To explore any fibrillation potential, the rats underwent serial electromyographic studies of bilateral gastrocnemius muscles over 5 weeks after burn injury. There were no denervation potentials either in muscles at sites distant from 20-25% and 30-35% of total body surface area burns or in muscles beneath the burn. In the present study on rats, thermal burn injury could not make fibrillation potentials in the electrodiagnostic study of muscles located near and distant from the burn site.

  14. Endurance training induces fiber type-specific revascularization in hindlimb skeletal muscles of rats with chronic heart failure

    PubMed Central

    Ranjbar, Kamal; Ardakanizade, Malihe; Nazem, Farzad

    2017-01-01

    Objective(s): Previous studies showed that skeletal muscle microcirculation was reduced in chronic heart failure. The aim of this study was to investigate the effects of endurance training on capillary and arteriolar density of fast and slow twitch muscles in rats with chronic heart failure. Materials and Methods: Four weeks after surgeries (left anterior descending (LAD) artery occlusion), chronic heart failure rats were divided into 3 groups: Sham (Sham, n=10); Sedentary (Sed, n=10); Exercise training (Ex, n=10). Ex group rats were subjected to endurance training in the form of treadmill running with moderate intensity for 10 weeks. Results: Exercise training significantly increased capillary density and capillary to fiber ratio (P<0.05) in slow twitch muscle, but didn’t change fast twitch muscle capillary density and capillary to fiber ratio. Furthermore, arteriolar density in fast twitch muscle increased remarkably (P<0.05) in response to training, but slow twitch muscle arteriolar density did not change in response to exercise in chronic heart failure rats. HIF-1 increased (P<0.01) but VEGF and FGF-2 mRNA did not change in slow twitch muscle after training. In fast twitch muscle, HIF-1 mRNA increased (P<0.05), and VEGF and angiostatin decreased (P<0.01) significantly after training. Conclusion: Endurance training ameliorates fast and slow twitch muscle revascularization non-uniformly in chronic heart failure rats by increasing capillary density in slow twitch muscle and arteriolar density in fast twitch muscle. The difference in revascularization at slow and fast twitch muscles may be induced by the difference in angiogenic and angiostatic gene expression response to endurance training. PMID:28133530

  15. Histopathological influence of alkaline ionized water on myocardial muscle of mother rats.

    PubMed

    Watanabe, T; Shirai, W; Pan, I; Fukuda, Y; Murasugi, E; Sato, T; Kamata, H; Uwatoko, K

    1998-12-01

    We have reported that a marked necrosis and subsequent fibrosis of myocardium occurred among male rats 15 weeks old given alkaline ionized water (AKW) during gestation and suckling periods, and after weaning. In this study, it was examined whether similar lesions would occur in mother rats which were given AKW from day zero of gestation to day 20 of lactation. The myocardial lesion in the mother rats given AKW showed cell infiltration, vacuolation and fibrosis in the papillary muscle of the left ventricle, as were observed in male rats of 15 weeks old. Myocardial degeneration may cause a leakage of potassium into the blood that results in a higher concentration of potassium in the blood in the test group than in that of the control group given tap water.

  16. Late onset muscle plasticity in the whisker pad of enucleated rats.

    PubMed

    Toscano-Márquez, Brenda; Martínez-Martínez, Eduardo; Manjarrez, Elías; Martínez, Lourdes; Mendoza-Torreblanca, Julieta; Gutiérrez-Ospina, Gabriel

    2008-10-14

    Blindness leads to a major reorganization of neural pathways associated with touch. Because incoming somatosensory information influences motor output, it is plausible that motor plasticity occurs in the blind. In this work, we evaluated this issue at the peripheral level in enucleated rats. Whisker muscles in enucleated rats 160 days of age or older showed increased cytochrome oxidase activity, capillary density, motor plate size, and amplitude of evoked field potentials as compared with their control counterparts. Such differences were not observed at ages 10 and 60 days, the capillary density was the exception being greater in the enucleated rat at the latter age. Interestingly, there was a trend to increased neurotrophin-3 concentrations in the whisker pads of enucleated rats throughout postnatal development. Our results show that neonatal enucleation leads to late onset plasticity of the whisker's motor system.

  17. Problems in analysis of data from muscles of rats flow in space

    NASA Technical Reports Server (NTRS)

    Tischler, Marc E.; Henriksen, Erik; Jacob, Stephan; Satarug, Soisungwan; Cook, Paul

    1988-01-01

    Comparison of hind-limb muscles of rats flown on Spacelab-3 or tail-traction-suspended showed that 11-17 h reloading postflight might have altered the results. Soleus atrophied; plantaris, gastrocnemius, and extensor digitorum longus grew slower; and tibialis anteiror grew normally. In both flight and simulated soleus and plantaris, higher tyrosine and greater glutamine/glutamate ratio indicated negative protein balance and increased glutamine production, respectively, relative to controls. Aspartate was lower in these muscles. Reloading generally decreased tyrosine, but increased aspartate and glutamine/glutamate. These data showed that 12 h of reloading after flight is characterized by reversal, to varying extents, of the effects of unloading.

  18. Problems in analysis of data from muscles of rats flown in space

    NASA Technical Reports Server (NTRS)

    Tischler, M. E.; Henriksen, E.; Jacob, S.; Satarug, S.; Cook, P.

    1988-01-01

    Comparison of hindlimb muscles of rats flown on Spacelab-3 or tail-traction-suspended showed that 11-17 h reloading post-flight might have altered the results. Soleus atrophied, plantaris, gastrocnemius and extensor digitorum longus grew slower, and tibialis anterior grew normally. In both flight and simulated soleus and plantaris, higher tyrosine and greater glutamine/glutamate ratio indicated negative protein balance and increased glutamine production, respectively, relative to controls. Aspartate was lower in these muscles. Reloading generally decreased tyrosine, but increased aspartate and glutamine/glutamate. These data showed that at 12 h of reloading after flight is characterized by reversal to varying extents of effects of unloading.

  19. Cancer cachexia: physical activity and muscle force in tumour-bearing rats.

    PubMed

    Toledo, Míriam; Busquets, Sílvia; Sirisi, Sònia; Serpe, Roberto; Orpí, Marcel; Coutinho, Joana; Martínez, Raquel; López-Soriano, Francisco J; Argilés, Josep M

    2011-01-01

    Rats bearing the Yoshida AH-130 ascites hepatoma are subjected to substantial weight loss, which is accompanied by anorexia at the end of the tumour cycle. Total physical activity (measured using the IR Actimeter system and Actitrack software) was determined during 11 days in control and tumour-bearing animals, skeletal muscle strength being also by the grip-strength test. The results presented clearly show that the presence of the tumour induces an earlier decrease in physical performance, which affects both skeletal muscle force and physical activity (both locomotor movements and stereotyped movements and distance travelled, among others parameters).

  20. Distribution of monocarboxylate transporters MCT1-MCT8 in rat tissues and human skeletal muscle.

    PubMed

    Bonen, Arend; Heynen, Miriam; Hatta, Hideo

    2006-02-01

    In the past decade, a family of monocarboxylate transporters (MCTs) have been identified that can potentially transport lactate, pyruvate, ketone bodies, and branched-chain ketoacids. Currently, 14 such MCTs are known. However, many orphan transporters exist that have transport capacities that remain to be determined. In addition, the tissue distribution of many of these MCTs is not well defined. Such a cataloging can, at times, begin to suggest the metabolic role of a particular MCT. Recently, a number of antibodies against selected MCTs (MCT1, -2, -4, and -5 to -8) have become commercially available. Therefore, we examined the protein expression of these MCTs in a large number of rat tissues (heart, skeletal muscle, skin, brain, testes, vas deferens, adipose tissue, liver, kidney, spleen, and pancreas), as well as in human skeletal muscle. Unexpectedly, many tissues coexpressed 4-5 MCTs. In particular, in rat skeletal muscle MCT1, MCT2, MCT4, MCT5, and MCT6 were observed. In human muscle, these same MCTs were present. We also observed a pronounced MCT7 signal in human muscle, whereas a very faint signal occurred for MCT8. In rat heart, which is an important metabolic sink for lactate, we confirmed that MCT1 and -2 were expressed. In addition, MCT6 and -8 were also prominently expressed in this tissue, although it is known that MCT8 does not transport aromatic amino acids or lactate. This catalog of MCTs in skeletal muscle and other tissues has revealed an unexpected complexity of coexpression, which makes it difficult to associate changes in monocarboxylate transport with the expression of a particular MCT. The differences in transport kinetics for lactate and pyruvate are only known for MCT1, -2 and -4. Transport kinetics remain to be established for many other MCTs. In conclusion, this study suggests that in skeletal muscle, as well as other tissues, lactate and pyruvate transport rates may not only involve MCT1 and -4, as other monocarboxylate transporters are

  1. Quantification of fibre type regionalisation: an analysis of lower hindlimb muscles in the rat

    PubMed Central

    WANG, L. C.; KERNELL, D.

    2001-01-01

    Newly developed concepts and methods for the quantification of fibre type regionalisation were used for comparison between all muscles traversing the ankle of the rat lower hindlimb (n = 12). For each muscle, cross-sections from the proximodistal midlevel were stained for myofibrillar ATPase and classified as type I (‘slow’) or II (‘fast’). For the 11 ‘fast’ muscles (i.e. all except soleus), the muscle outline and the position of each type I fibre were digitised for further computer processing. Two potentially independent aspects of type I fibre regionalisation were evaluated quantitatively: (1) the degree to which type I fibres were restricted to a limited portion of the total cross-sectional area (‘area-regionalisation’) ; (2) the extent and direction of the difference (if any) between the centre of the muscle cross-section and the calculated centre for the type I fibre cluster (‘vector regionalisation’). Statistical analysis showed that type I fibres were vector regionalised in practically all investigated muscles and area regionalised within most of them, the only consistent exceptions being peroneus brevis and peroneus digitorum 4, 5. In muscles with a high degree of area regionalisation the population of type I fibres also had a markedly eccentric intramuscular position (i.e. high vector regionalisation). A significant relationship was observed between the relative position of a muscle within the hindlimb (transverse plane) and the direction and degree of its type I fibre eccentricity. On average, the degree of type I fibre eccentricity was greater for muscles remote from the limb centre than for those situated more centrally. In addition, the intramuscular concentration of type I fibres was typically greatest towards the centre of the limb, the most striking exception being tibialis posterior. For the slow soleus muscle, which is centrally placed within the limb, our analysis concerned the type II fibres, which were found to be weakly

  2. [Structural changes in the soleus muscle of rats on the Kosmos-series biosatellites and in hypokinesia].

    PubMed

    Il'ina-Kakueva, E I; Portugalov, V V

    1981-01-01

    Structural changes in the soleus muscle of rats used in flight and synchronous experiments of the Cosmos program and hypokinetic studies have been investigated. It is hypothesized that focal edema and dystrophic changes observed in flight, synchronous and hypokinetic rats can be caused by circulation disorders of different etiology. In flight and synchronous rats they develop two days postflight due to the deconditioning of the muscle tissue and intraorgan vascular system which fail to meet the requirements after transition from 0 g to 1 g. In hypokinetic rats circulation disorders occur on the first experimental day due to mechanical causes (paws are pressed against the cage floor impeding venous outflow) and muscle pump deficiency. In all cases circulation disorders seem to be associated with peculiar features of angioarchitectonics of the soleus muscle.

  3. Molecular and physiological events in respiratory muscles and blood of rats exposed to inspiratory threshold loading.

    PubMed

    Domínguez-Álvarez, Marisol; Sabaté-Brescó, Marina; Vilà-Ubach, Mònica; Gáldiz, Juan B; Alvarez, Francisco J; Casadevall, Carme; Gea, Joaquim; Barreiro, Esther

    2014-05-01

    High-intensity exercise induces oxidative stress and inflammatory events in muscles. Tumor necrosis factor (TNF)-α may alter muscle protein metabolism or promote muscle regeneration. We hypothesized that a program of noninvasive chronic inspiratory loading of different intensities induces a differential pattern of physiological, molecular, and cellular events within rat diaphragms. Antioxidants and TNF-α blockade may influence those events. In the diaphragm, gastrocnemius, and blood of rats exposed to high-intensity inspiratory threshold loads (2 hour every 24 hours for 14 days), with and without treatment with N-acetyl cysteine or infliximab (anti-TNF-α antibody), inflammatory cells and cytokines, superoxide anion production, myogenesis markers, and muscle structure were explored. In all animals, maximum inspiratory pressure (MIP) and body weight were determined. High-intensity inspiratory loading for 2 weeks caused a decline in MIP and body weight, and in the diaphragm induced a reduction in fast-twitch fiber proportions and sizes, whereas inflammatory cells and cytokine levels, including TNF-α immunohistochemical expression, superoxide anion, internal nuclei counts, and markers of myogenesis were increased. Blockade of TNF-α improved respiratory muscle function and structure, and animal weight, and, in the diaphragm, reduced inflammatory cell numbers and superoxide anion production drastically while inducing larger increases in protein and messenger RNA levels and immunohistochemical expression of TNF-α, internal nuclei, and markers of muscle regeneration. Blunting of TNF-α also induced a reduction in blood inflammatory cytokines and superoxide anion production. We conclude that TNF-α synthesized by inflammatory cells or myofibers could have differential effects on muscle structure and function in response to chronic, noninvasive, high-intensity inspiratory threshold loading.

  4. Sulforaphane treatment protects skeletal muscle against damage induced by exhaustive exercise in rats.

    PubMed

    Malaguti, Marco; Angeloni, Cristina; Garatachea, Nuria; Baldini, Marta; Leoncini, Emanuela; Collado, Pilar S; Teti, Gabriella; Falconi, Mirella; Gonzalez-Gallego, Javier; Hrelia, Silvana

    2009-10-01

    Sulforaphane (SF), one of the most important isothiocyanates in the human diet, present in cruciferous vegetables, is known to have chemopreventive activities in different tissues. No data are available on its effects in the prevention of skeletal muscle damage. In this study, we investigated the potential protective effects of SF treatment on muscle damage and oxidative stress induced by an acute bout of exhaustive exercise in rats. Male Wistar rats were treated with SF (25 mg/kg body wt ip) for 3 days before undergoing an acute exhaustive exercise protocol in a treadmill (+7% slope and 24 m/min). Acute exercise resulted in a significant increase in plasma lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) activities. It also resulted in a significant increase in thiobarbituric acid-reactive substances, in a significant decrease in tissue total antioxidant capacity, and in a significant decrease in NAD(P)H:quinone oxidoreductase 1 (NQO1) expression and activity in vastus lateralis muscle. SF treatment significantly increased muscle NQO1, glutathione-S-transferase, and glutathione reductase expression and activity, with no effect on glutathione peroxidase and thioredoxin reductase. The observed SF-induced upregulation of phase II enzymes was accompanied by a significant increase in nuclear erythroid 2 p45-related factor 2 expression and correlated with a significant increase in total antioxidant capacity and a decrease in plasma LDH and CPK activities. Our data demonstrate that SF acts as an indirect antioxidant in skeletal muscle and could play a critical role in the modulation of the muscle redox environment, leading to the prevention of exhaustive exercise-induced muscle damage.

  5. Effect of short-term gravitational unloading on rat and mongolian gerbil muscles.

    PubMed

    Ogneva, Irina V; Kurushin, Vsevolod A; Altaeva, Erzhena G; Ponomareva, Elena V; Shenkman, Boris S

    2009-12-01

    Gravitational unloading leads to destructive changes in the structure and function of muscle fibers. However, the role of the EMG activity level is still unclear. We measured changes caused by one- and three-day hypogravity in the following muscles: Soleus (Sol), Tibialis anterior (TA) and Gastrocnemius c.m. (MG). We used Wistar rats and Mongolian gerbils. The following parameters were assessed: the specific force of contraction of isolated fibers by tensometry, the transverse stiffness of the contractile apparatus by atomic force microscopy, and the calcium content by Fluo-4. We detected the accumulation of calcium ions in all muscles even after one-day unloading. In Sol this effect was more significant than in other muscles. After one-day of hypogravity we detected an increase in the specific force in all muscle types and species. Meanwhile, the transverse stiffness of the contractile apparatus, M-band and Z-disc increased only in fast muscles but not in Sol. After three-days of unloading, the specific force in Sol decreased, and the transverse stiffness of the contractile apparatus behaved in the same way as the force. The specific tension of fast muscle fibers decreased significantly in comparison with one-day unloading. In addition, the transverse stiffness of some areas of MG had a tendency to decrease in comparison to "one-day" unloading, although there was no such a tendency in the fibers of TA. In Mongolian gerbils the tendencies were the same as in the rats, but showed less dramatic changes. The reduction in the magnitude of changes in the Sol-MG-TA series correlates with EMG activity.

  6. The Rho-related protein Rnd1 inhibits Ca2+ sensitization of rat smooth muscle

    PubMed Central

    Loirand, Gervaise; Cario-Toumaniantz, Chrystelle; Chardin, Pierre; Pacaud, Pierre

    1999-01-01

    The small GTP-binding Rho proteins are involved in the agonist-induced Ca2+ sensitization of smooth muscle. The action and the expression of Rnd1, a new member of the Rho protein family constitutively bound to GTP, has been studied in rat smooth muscle. Recombinant prenylated Rnd1 (0.01-0.1 mg ml−1) dose dependently inhibited carbachol- and GTPγS-induced Ca2+ sensitization in β-escin-permeabilized ileal smooth muscle strips but had no effect on the tension at submaximal [Ca2+] (pCa 6.3). Rnd1 inhibited GTPγS-induced tension without shifting the dose-response curves to GTPγS. pCa-tension relationships were not modified by Rnd1 and the rise in tension induced through the inhibition of myosin light chain phosphatase by calyculin A was not affected by Rnd1. The Ca2+ sensitization induced by recombinant RhoA was completely abolished when RhoA and Rnd1 were applied together. Rnd1 was expressed at a low level in membrane fractions prepared from intestinal or arterial smooth muscles. The expression of Rnd1 was strongly increased in ileal and aortic smooth muscle from rats treated with progesterone or oestrogen. Progesterone-treated ileal muscle strips showed a decrease in agonist-induced Ca2+ sensitization. The present study shows that (i) Rnd1 inhibits agonist- and GTPγS-induced Ca2+ sensitization of smooth muscle by specifically interfering with a RhoA-dependent mechanism and (ii) an increase in Rnd1 expression may account, at least in part, for the steroid-induced decrease in agonist-induced Ca2+ sensitization. PMID:10200428

  7. Neurolytic celiac plexus block enhances skeletal muscle insulin signaling and attenuates insulin resistance in GK rats.

    PubMed

    Li, Jun; Chen, Tao; Li, Kun; Yan, Hongtao; Li, Xiaowei; Yang, Yun; Zhang, Yulan; Su, Bingyin; Li, Fuxiang

    2016-05-01

    Non-insulin-dependent diabetes mellitus (NIDDM) is associated with chronic inflammatory activity and disrupted insulin signaling, leading to insulin resistance (IR). The present study investigated the benefits of neurolytic celiac plexus block (NCPB) on IR in a rat NIDDM model. Goto-Kakizaki rats fed a high-fat, high-glucose diet to induce signs of NIDDM were randomly divided into NCPB and control groups; these received daily bilateral 0.5% lidocaine or 0.9% saline injections into the celiac plexus, respectively. Following 14 and 28 daily injections, rats were subject to oral glucose tolerance tests (OGTTs) or sacrificed for the analysis of serum free fatty acids (FFAs), serum inflammatory cytokines and skeletal muscle insulin signaling. Compared with controls, rats in the NCPB group demonstrated significantly (P<0.05) lower baseline, 60-min and 120-min OGTT values, lower 120-min serum insulin, lower IR [higher insulin sensitivity index (ISI1) and lower ISI2) and lower serum FFAs, tumor necrosis factor-α, interleukin (IL)-1β and IL-6. Conversely, NCPB rats exhibited higher basal and insulin-stimulated skeletal muscle glucose uptake and higher skeletal muscle insulin receptor substrate-1 (IRS-1) and glucose transporter type 4 expression. There were no differences between the groups in insulin receptor β (Rβ) or Akt expression; however Rβ-Y1162/Y1163 and Akt-S473 phosphorylation levels were higher and IRS-1-S307 phosphorylation were lower in NCPB rats than in the controls. These results indicate that NCPB improved insulin signaling and reduced IR, possibly by inhibiting inflammatory cytokine release.

  8. Prostanoid receptors mediating contraction in rat, macaque and human bladder smooth muscle in vitro.

    PubMed

    Root, James A; Davey, Dorren A; Af Forselles, Kerry J

    2015-12-15

    Selective prostaglandin EP1 antagonists have been suggested for the treatment of bladder dysfunction. This study assessed the contractile prostanoid receptor subtypes in human and non-human bladder in vitro. Classical tissue bath studies were conducted using bladder strips exposed to prostanoid agonists and antagonists. Prostaglandin E2 (PGE2) contracted rat, macaque and human bladder smooth muscle strips (pEC50 7.91±0.06 (n=7), 6.40±0.13 (n=7), and 6.07±0.11 (n=5), respectively). The EP1 receptor antagonist, PF2907617 (300nM), caused a rightward shift of the PGE2 concentration-response curve in the rat bladder only (pKB 8.40±0.15, n=3). PGE2 responses in rat and macaque bladders, but not human, were antagonised by the EP3 antagonist CJ24979 (1µM). Sulprostone, a mixed EP1/EP3/FP receptor agonist, induced potent contractions of rat bladder muscle (pEC50 7.94±0.31, n=6). The FP receptor agonist, prostaglandin F2α (PGF2α), induced bladder contraction in all species tested, but with a lower potency in rat. The selective FP receptor agonist latanoprost caused potent contractions of macaque and human bladder strips only. SQ29548, a selective TP antagonist, and GW848687X, a mixed EP1/TP antagonist caused rightward shifts of the concentration-response curves to the selective TP agonist, U46619 (pKB estimates 8.53±0.07 and 7.56±0.06, n=3, respectively). Responses to U46619 were absent in rat preparations. These data suggest significant species differences exist in bladder contractile prostanoid receptor subtypes. We conclude that the EP1 subtype does not represent the best approach to the clinical treatment of bladder disorders targeting inhibition of smooth muscle contraction.

  9. Neurolytic celiac plexus block enhances skeletal muscle insulin signaling and attenuates insulin resistance in GK rats

    PubMed Central

    LI, JUN; CHEN, TAO; LI, KUN; YAN, HONGTAO; LI, XIAOWEI; YANG, YUN; ZHANG, YULAN; SU, BINGYIN; LI, FUXIANG

    2016-01-01

    Non-insulin-dependent diabetes mellitus (NIDDM) is associated with chronic inflammatory activity and disrupted insulin signaling, leading to insulin resistance (IR). The present study investigated the benefits of neurolytic celiac plexus block (NCPB) on IR in a rat NIDDM model. Goto-Kakizaki rats fed a high-fat, high-glucose diet to induce signs of NIDDM were randomly divided into NCPB and control groups; these received daily bilateral 0.5% lidocaine or 0.9% saline injections into the celiac plexus, respectively. Following 14 and 28 daily injections, rats were subject to oral glucose tolerance tests (OGTTs) or sacrificed for the analysis of serum free fatty acids (FFAs), serum inflammatory cytokines and skeletal muscle insulin signaling. Compared with controls, rats in the NCPB group demonstrated significantly (P<0.05) lower baseline, 60-min and 120-min OGTT values, lower 120-min serum insulin, lower IR [higher insulin sensitivity index (ISI1) and lower ISI2) and lower serum FFAs, tumor necrosis factor-α, interleukin (IL)-1β and IL-6. Conversely, NCPB rats exhibited higher basal and insulin-stimulated skeletal muscle glucose uptake and higher skeletal muscle insulin receptor substrate-1 (IRS-1) and glucose transporter type 4 expression. There were no differences between the groups in insulin receptor β (Rβ) or Akt expression; however Rβ-Y1162/Y1163 and Akt-S473 phosphorylation levels were higher and IRS-1-S307 phosphorylation were lower in NCPB rats than in the controls. These results indicate that NCPB improved insulin signaling and reduced IR, possibly by inhibiting inflammatory cytokine release. PMID:27168847

  10. Effect of taurine depletion on excitation-contraction coupling and Cl- conductance of rat skeletal muscle.

    PubMed

    De Luca, A; Pierno, S; Camerino, D C

    1996-01-25

    The pharmacological action of taurine on skeletal muscle is to stabilize sarcolemma by increasing macroscopic conductance to Cl- (GCl), whereas a proposed physiological role for the amino acid is to modulate excitation-contraction coupling mechanism via Ca2+ availability. To get insight in the physiological role of taurine in skeletal muscle, the effects of its depletion were evaluated on voltage threshold for mechanical activation and GCl with the two intracellular microelectrode method in 'point' voltage clamp mode and current clamp mode, respectively. The experiments were performed on extensor digitorum longus muscle fibers from rats depleted of taurine by a chronic 4 week treatment with guanidinoethane sulfonate, a known inhibitor of taurine transporter. The treatment significantly modified the mechanical threshold of striated fibers; i.e. at each pulse duration they needed significantly less depolarization to contract and the fitted rheobase voltage was more negative by 10 mV with respect to untreated muscle fibers. In parallel, the treatment with guanidinoethane sulfonate produced a significant 40% lowering of GCl. In vitro application of 60 mM of taurine to such depleted muscles almost completely restored the mechanical threshold and increased GCl even above the value of untreated control. However, in vitro application of 60 mM of either taurine or guanidinoethane sulfonate to untreated control muscles did not cause any change of the mechanical threshold but increased GCl by 40% and 21%, respectively. Furthermore, 100 microM of the S-(-) enantiomer of 2-(p-chlorophenoxy)propionic acid almost fully blocked GCl but did not produce any change in the mechanical threshold of normal muscle fibers. The present results show that the large amount of intracellular taurine plays a role in the excitation-contraction coupling mechanism of striated muscle fibers. This action is independent from any effect involving muscle Cl- channels, but it is likely mediated by the

  11. Effect of Intramuscular Protons, Lactate, and ATP on Muscle Hyperalgesia in Rats.

    PubMed

    Gregory, Nicholas S; Whitley, Phillip E; Sluka, Kathleen A

    2015-01-01

    Chronic muscle pain is a significant health problem leading to disability[1]. Muscle fatigue can exacerbate muscle pain. Metabolites, including ATP, lactate, and protons, are released during fatiguing exercise and produce pain in humans. These substances directly activate purinergic (P2X) and acid sensing ion channels (ASICs) on muscle nociceptors, and when combined, produce a greater increase in neuron firing than when given alone. Whether the enhanced effect of combining protons, lactate, and ATP is the sum of individual effects (additive) or more than the sum of individual effects (synergistic) is unknown. Using a rat model of muscle nociceptive behavior, we tested each of these compounds individually over a range of physiologic and supra-physiologic concentrations. Further, we combined all three compounds in a series of dilutions and tested their effect on muscle nociceptive behavior. We also tested a non-hydrolyzable form of ATP (α,β-meATP) alone and in combination with lactate and acidic pH. Surprisingly, we found no dose-dependent effect on muscle nociceptive behavior for protons, lactate, or ATP when given alone. We similarly found no effect after application of each two-metabolite combination. Only pH 4 saline and α,β-meATP produced hyperalgesia when given alone. When all 3 substances were combined, however, ATP (2.4μm), lactate (10mM), and acidic pH (pH 6.0) produced an enhanced effect greater than the sum of the effects of the individual components, i.e. synergism. α,β me ATP (3nmol), on the other hand, showed no enhanced effects when combined with lactate (10mM) or acidic pH (pH 6.0), i.e. additive. These data suggest that combining fatigue metabolites in muscle produces a synergistic effect on muscle nociception.

  12. Matching of sarcoplasmic reticulum and contractile properties in rat fast- and slow-twitch muscle fibres.

    PubMed

    Trinh, Huong H; Lamb, Graham D

    2006-07-01

    1. The twitch characteristics (fast-twitch or slow-twitch) of skeletal muscle fibres are determined not only by the contractile apparatus properties of the fibre, but also by the time-course of Ca2+ release and re-uptake by the sarcoplasmic reticulum (SR). The present study examined, in individual fibres from non-transforming muscle of the rat, whether particular SR properties are matched to the contractile apparatus properties of the fibre, in particular in the case of fibres with fast-twitch contractile apparatus located in a slow-twitch muscle, namely the soleus. 2. Force was recorded in single, mechanically skinned fibres from extensor digitorum longus (EDL), gastrocnemius, peroneus longus and soleus muscles. Using repeated cycles in which the SR was emptied of all releasable Ca2+ and then reloaded, it was possible to determine the relative amount of Ca2+ present in the SR endogenously, the maximum SR capacity and the rate of Ca2+ loading. The sensitivity of the contractile apparatus to Ca2+ and Sr2+ was used to classify the fibres as fast-twitch (FT), slow-twitch (ST) or mixed (< 3% of the fibres examined) and thereby identify the likely troponin C and myosin heavy chain types present. 3. There was no significant difference in SR properties between the groups of FT fibres obtained from the four different muscles, including soleus. Despite some overlap in the SR properties of individual fibres between the FT and ST groups, the properties of the FT fibres in all four muscles studied were significantly different from those of the ST and mixed fibres. 4. In general, in FT fibres the SR had a larger capacity and the endogenous Ca2+ content was a relatively lower percentage of maximum compared with ST fibres. Importantly, in terms of their SR properties, FT fibres from soleus muscle more closely resembled FT fibres from other muscles than they did ST fibres from soleus muscle.

  13. Impact of dietary nitrate supplementation via beetroot juice on exercising muscle vascular control in rats.

    PubMed

    Ferguson, Scott K; Hirai, Daniel M; Copp, Steven W; Holdsworth, Clark T; Allen, Jason D; Jones, Andrew M; Musch, Timothy I; Poole, David C

    2013-01-15

    Dietary nitrate (NO(3)(-)) supplementation, via its reduction to nitrite (NO(2)(-)) and subsequent conversion to nitric oxide (NO) and other reactive nitrogen intermediates, reduces blood pressure and the O(2) cost of submaximal exercise in humans. Despite these observations, the effects of dietary NO(3)(-) supplementation on skeletal muscle vascular control during locomotory exercise remain unknown. We tested the hypotheses that dietary NO(3)(-) supplementation via beetroot juice (BR) would reduce mean arterial pressure (MAP) and increase hindlimb muscle blood flow in the exercising rat. Male Sprague-Dawley rats (3-6 months) were administered either NO(3)(-) (via beetroot juice; 1 mmol kg(-1) day(-1), BR n = 8) or untreated (control, n = 11) tap water for 5 days. MAP and hindlimb skeletal muscle blood flow and vascular conductance (radiolabelled microsphere infusions) were measured during submaximal treadmill running (20 m min(-1), 5% grade). BR resulted in significantly lower exercising MAP (control: 137 ± 3, BR: 127 ± 4 mmHg, P < 0.05) and blood [lactate] (control: 2.6 ± 0.3, BR: 1.9 ± 0.2 mm, P < 0.05) compared to control. Total exercising hindlimb skeletal muscle blood flow (control: 108 ± 8, BR: 150 ± 11 ml min(-1) (100 g)(-1), P < 0.05) and vascular conductance (control: 0.78 ± 0.05, BR: 1.16 ± 0.10 ml min(-1) (100 g)(-1) mmHg(-1), P < 0.05) were greater in rats that received BR compared to control. The relative differences in blood flow and vascular conductance for the 28 individual hindlimb muscles and muscle parts correlated positively with their percentage type IIb + d/x muscle fibres (blood flow: r = 0.74, vascular conductance: r = 0.71, P < 0.01 for both). These data support the hypothesis that NO(3)(-) supplementation improves vascular control and elevates skeletal muscle O(2) delivery during exercise predominantly in fast-twitch type II muscles, and provide a potential mechanism by which NO(3)(-) supplementation improves metabolic control.

  14. Distinguishing effects of anemia and muscle iron deficiency on exercise bioenergetics in the rat

    SciTech Connect

    Davies, K.J.A.; Donovan, C.M.; Refino, C.J.; Brooks, G.A.; Packer, L.; Dallman, P.R.

    1984-06-01

    Three weeks of dietary iron deficiency in weanling rats resulted in anemia (Hb, 39 vs 14.2 g/dl in controls) and decreased oxidative capacities of skeletal muscle (as much as 90% below control values). Whole-animal maximal O/sub 2/ consumption V/sub 0/sub 2///sub max//, measured in a brief treadmill run of progressively increasing work load, was approx.50% lower for iron-deficient rats than for controls, and maximal endurance capacity (time to exhaustion in a separate treadmill run at a constant, sub- V/sub 0/sub 2///sub max// work load) was 90% lower from iron-deficient rats than for controls. Exchange transfusion with packed erythrocytes or plasma, was used to adjust Hb to an intermediate concentration of approximately 9.5 g/dl in both iron-deficient and control rats. This procedure corrected the V/sub 0/sub 2///sub max// of iron-deficient rats to within 15% of control values, whereas endurance capacity showed no improvement. Our experimental dissociation of V/sub 0/sub 2///sub max/// and endurance capacity provides further evidence that V/sub 0/sub 2///sub max// is not the sole determinant of endurance. We propose that defects in V/sub 0/sub 2///sub max// during iron deficiency result primarily from diminished O/sub 2/ delivery, whereas decreased endurance capacity reflects impaired muscle mitochondrial function.

  15. Effect of dietary lipid, carnitine and exercise on lipid profile in rat blood, liver and muscle.

    PubMed

    Karanth, Jyothsna; Jeevaratnam, K

    2009-09-01

    Aim of this study was to investigate the influence of physical exercise on effects of the daily intake of vegetarian diet of either vegetable hydrogenated fat (HF) or peanut oil (PO) with or without carnitine on the lipid profile. Eight groups of male Wistar rats were fed HF-diet (4 groups) or PO-diet (4 groups), with or without carnitine for 24 weeks. One group for each diet acted as sedentary control while the other groups were allowed swimming for 1 hr a day, 6 days/week, for 24 weeks. Plasma triglycerides (TG), total cholesterol (TC), HDL-cholesterol, free fatty acids (FFA), liver and thigh muscle glycogen, total fat (TF), TG, TC and FFA were analyzed. HF-fed rats showed significantly increased plasma TC, VLDL+LDL-cholesterol and TG compared to PO-fed rats, wherein a lowered plasma TC, TG levels in all the groups with significantly increased liver cholesterol and decreased muscle cholesterol was observed. Physical exercise of moderate intensity reduced plasma TC and TG accompanied by significantly reduced tissue TG and cholesterol while FFA and glycogen increased in all the groups. The influence of exercise was less pronounced in carnitine supplemented rats since carnitine could significantly reduce TG in plasma and tissues of sedentary rats. Results from the present study showed that the intake of HF diet significantly increased the plasma and tissue lipid profile and MUFA-rich diet or carnitine supplementation and/or exercise may ameliorate the deleterious effects of HF.

  16. Biochemical and histochemical changes in energy supply enzyme pattern of muscles of the rat during old age.

    PubMed

    Bass, A; Gutmann, E; Hanzlíková, V

    1975-01-01

    Senile muscles of the rat (28-36 months) show loss of overall activity of glycolytic and aerobic enzymes. However, there is a differential loss and shift of enzyme activity pattern in the three types of muscles. The extensor digitorum longus (EDL) and diaphragm show a decrease of ratios of glycolytic to aerobic-oxidative enzymes. This shift to a more oxidative type of metabolism is not observed in the soleus muscle. Decrease of enzyme activities is least marked in the diaphragm muscle. Biochemical analysis shows a trend to levelling out of metabolic differences between the different muscle types. This trend of 'dedifferentiation' is most marked when comparing EDL and soleus, least marked when comparing EDL and diaphragm muscle. The histochemical analysis shows a shift from the original mixed to a more uniform pattern of muscle fibres in the EDL and soleus muscle; this levelling-out of differences between enzymatic activities of different muscle fibres is not observed in the diaphragm muscle. Preferential atrophy and loss of ATPase activity in II muscle fibres in the soleus muscle and the occurrence of 'type grouping' are further characteristic features of senile muscle change. The findings show general (i.e. loss of enzyme activities) and differential trends of biochemical and histochemical enzyme changes in different types of muscles.

  17. Glucose-dependent insulinotropic polypeptide directly induces glucose transport in rat skeletal muscle.

    PubMed

    Snook, Laelie A; Nelson, Emery M; Dyck, David J; Wright, David C; Holloway, Graham P

    2015-08-01

    Several gastrointestinal proteins have been identified to have insulinotropic effects, including glucose-dependent insulinotropic polypeptide (GIP); however, the direct effects of incretins on skeletal muscle glucose transport remain largely unknown. Therefore, the purpose of the current study was to examine the role of GIP on skeletal muscle glucose transport and insulin signaling in rats. Relative to a glucose challenge, a mixed glucose+lipid oral challenge increased circulating GIP concentrations, skeletal muscle Akt phosphorylation, and improved glucose clearance by ∼35% (P < 0.05). These responses occurred without alterations in serum insulin concentrations. In an incubated soleus muscle preparation, GIP directly stimulated glucose transport and increased GLUT4 accumulation on the plasma membrane in the absence of insulin. Moreover, the ability of GIP to stimulate glucose transport was mitigated by the addition of the PI 3-kinase (PI3K) inhibitor wortmannin, suggesting that signaling through PI3K is required for these responses. We also provide evidence that the combined stimulatory effects of GIP and insulin on soleus muscle glucose transport are additive. However, the specific GIP receptor antagonist (Pro(3))GIP did not attenuate GIP-stimulated glucose transport, suggesting that GIP is not signaling through its classical receptor. Together, the current data provide evidence that GIP regulates skeletal muscle glucose transport; however, the exact signaling mechanism(s) remain unknown.

  18. Immunocytochemical localization of taurine in different muscle cell types of the dog and rat.

    PubMed

    Lobo, M V; Alonso, F J; Martin del Rio, R

    2000-01-01

    The presence and distribution of the amino acid taurine in different muscle cell types of the dog and rat was examined by immunocytochemical methods. The light microscope study revealed that smooth muscle cells were similarly immunoreactive for taurine, whereas skeletal muscle fibres showed wide differences in taurine immunoreactivity among individual cells. Some skeletal fibres were strongly immunoreactive whereas others did not display immunolabelling. Mononucleated satellite cells, found adjacent to skeletal fibres in a quiescent stage, were also immunostained. Other myoid cells, such as testicular peritubular cells showed a cytoplasmic and a nuclear pool of taurine. By means of electron microscope immunolabelling, the subcellular localization of taurine was studied in vascular and visceral smooth muscle cells. Taurine was present in most subcellular compartments and frequently appeared randomly distributed. Taurine was localized on myofilaments, dense bodies, mitochondria, the plasma membrane and the cell nucleus. Moreover, the labelling density within individual smooth muscle cells was variable and depended on the state of contraction of each single fibre. Contracted cells showed a higher density of gold particles than relaxed cells. Unmyelinated nerve fibres, found adjacent to smooth muscle cells from the muscularis mucosae and the lamina propria of the stomach, were unstained or poorly stained.

  19. Training differentially regulates elastin level and proteolysis in skeletal and heart muscles and aorta in healthy rats

    PubMed Central

    Gilbert, Anna; Wyczalkowska-Tomasik, Aleksandra; Zendzian-Piotrowska, Malgorzata; Czarkowska-Paczek, Bozena

    2016-01-01

    ABSTRACT Exercise induces changes in muscle fibers and the extracellular matrix that may depend on elastin content and the activity of proteolytic enzymes. We investigated the influence of endurance training on the gene expression and protein content and/or activity of elastin, elastase, cathepsin K, and plasmin in skeletal and heart muscles and in the aorta. Healthy rats were randomly divided into untrained (n=10) and trained (n=10; 6 weeks of endurance training with increasing load) groups. Gene expression was evaluated via qRT-PCR. Elastin content was measured via enzyme-linked immunosorbent assay and enzyme activity was measured fluorometrically. Elastin content was significantly higher in skeletal (P=0.0014) and heart muscle (P=0.000022) from trained rats versus untrained rats, but not in the aorta. Although mRNA levels in skeletal muscle did not differ between groups, the activities of elastase (P=0.0434), cathepsin K (P=0.0343) and plasmin (P=0.000046) were higher in trained rats. The levels of cathepsin K (P=0.0288) and plasminogen (P=0.0005) mRNA were higher in heart muscle from trained rats, but enzyme activity was not. Enzyme activity in the aorta did not differ between groups. Increased elastin content in muscles may result in better adaption to exercise, as may remodeling of the extracellular matrix in skeletal muscle. PMID:27069251

  20. Proteomic studies of rat tibialis anterior muscle during postnatal growth and development.

    PubMed

    Sun, Hualin; Zhu, Ting; Ding, Fei; Hu, Nan; Gu, Xiaosong

    2009-12-01

    In this study, a proteomic analysis consisting of two-dimensional gel electrophoresis and MALDI-TOF/TOF mass spectrometry was accomplished to investigate the complex protein expression patterns in rat tibialis anterior muscle during postnatal 3-month period. We determined the time-dependent expression alterations of 107 protein spots, among which 53 protein spots were identified. These identified proteins included skeletal contractile proteins, metabolic enzymes, chaperone, intermediate filament, and signal transduction proteins. The time-dependent expression of three proteins, such as Mylpf, desmin, and RKIP, was confirmed by Western blot analysis and immunohistochemistry. The functional implication of these expression changes was also discussed. We further analyzed the linkage and interactions among the differentially expressed proteins (MAPK1, RKIP, AHSG, etc.). Collectively, the results might add to the understanding of the molecular mechanisms regulating postnatal growth and development of rat tibialis anterior muscle.

  1. Altered distribution of mitochondria in rat soleus muscle fibers after spaceflight

    NASA Technical Reports Server (NTRS)

    Bell, Gordon J.; Martin, Thomas P.; Il'ina-Kakueva, E. I.; Oganov, V. S.; Edgerton, V. R.

    1992-01-01

    The effect of an exposure to microgravity on the distribution of the succinate dehydrogenase (SDH) activity throughout the soleus muscle fibers was investigated by measuring SDH activity throughout the cross section of 20-30 fibers each of the slow-twitch oxidative and fast-twitch oxidative-glycolytic types of fibers in rats exposed to 12.5 days in space aboard Cosmos 1887. It was found that, after the spaceflight, the entire regional distribution of SDH activity was significantly altered (as compared to ground controls) in the slow-twitch oxidative fibers, whereas the fast-twitch oxidative-glycolytic fibers from muscles of flown rats exhibited a significantly lower SDH activity only in their subsarcolemmal region.

  2. Substrates for protein kinase C in a cell free preparation of rat aorta smooth muscles

    SciTech Connect

    Nakaki, T.; Wise, B.C.; Chuang, D.M.

    1988-01-01

    Protein phosphorylation has been studied in a cell free system of rat aorta smooth muscles. Addition of Ca/sup 2 +/ caused phosphorylation of several proteins. The addition of phosphatidylserine or calmodulin together with Ca/sup 2 +/ further increased the phosphorylation of proteins with apparent molecular weights of 20 and 92.5 kilodaltons. The activators of protein kinase C, 12-0-tetradecanoylphorbol-13-acetate and 1,2-diolein, increased phosphorylation of the protein bands of similar molecular weight to those increased by phosphatidylserine in the presence of Ca/sup 2 +/, whereas the biologically inactive phorbol ester, 4 ..cap alpha..-phorbol-12,13 didecanoate (4 ..cap alpha.. PDD) failed to change the pattern of protein phosphorylation. These results show that proteins present in smooth muscle of rat aorta with molecular weights of 20 and 92.5 kilodaltons are substrates for protein kinase C.

  3. Up-regulation of muscle uncoupling protein 3 gene expression by calcium channel blocker, benidipine hydrochloride in rats.

    PubMed

    Sakane, Naoki; Kotani, Kazuhiko; Hioki, Chizuko; Yoshida, Toshihide; Kawada, Teruo

    2007-12-01

    To examine whether benidipine hydrochloride, one of the calcium channel blockers, up-regulate uncoupling protein 3 (UCP3) expression in two skeletal muscles (gastrocnemius and soleus) in rats. Wistar rats were treated orally with benidipine hydrochloride at 4 mg/kg for 7 days. Blood pressure was measured after 4 days. At the end of experiments, the rats were weighed, and brown adipose tissue (BAT) and skeletal muscles (gastrocnemius and soleus muscles) were removed. The mRNA levels of uncoupling protein 1 (UCP1) and UCP3 were measured using the real-time quantitative reverse transcription-polymerase chain reaction method. Benidipine reduced body weight and also had a hypotensive effect. In rats treated with benidipine, UCP1 mRNA levels were significantly increased 1.4-fold in BAT, and UCP3 mRNA levels in BAT and gastrocnemius muscle were significantly increased 1.7 and 3.0-fold, respectively, compared with the control rats. There was no difference in UCP3 mRNA levels in soleus muscle between the two groups. We concluded that benidipine up-regulates not only UCP1 gene expression in BAT but also UCP3 gene expression in BAT and gastrocnemius muscle, which may contribute to thermogenesis in rats.

  4. Motor units in a skeletal muscle of neonatal rat: mechanical properties and weak neuromuscular transmission.

    PubMed Central

    Jones, S P; Ridge, R M

    1987-01-01

    1. Isometric twitch and tetanic tensions were recorded from whole muscles and single motor units in isolated fourth deep lumbrical muscles from neonatal rats (most at 3-5 days old) and from older rats of various ages. 2. Whole-muscle time to peak contraction reduced from about 120 ms at birth to about 20-25 ms at 20 days and older. 3. The number of motor units in the muscle was constant with age (eleven on average) and there was no significant branching of motor axons below the common peroneal nerve branching point in the thigh. 4. In the 3-5 days age range, mean twitch:tetanus ratio for whole muscles was 0.299 and for single units was 0.177. As a consequence, mean motor unit size (as a percentage of whole-muscle tension) was greater for tetani (29.7%) than for twitches (19.9%). This was not the case in muscles from animals 22 days or older. Evidence is given that the cause of this is low junctional efficacy in some neuromuscular junctions in neonatal muscle. Intracellular recordings supported this view. 5. The relationships of motor-unit size to the contraction time, to the ratio of contraction time:half-relaxation time, and to fatigue index are given. There was no indication of clear segregation of motor units into more than one population, but it is concluded that small motor units are more likely to contain a higher proportion of slowly contracting, fatigue-resistant fibres than large units. 6. The level of overlap by axons in the lateral plantar nerve onto muscle fibres in a single sural nerve motor unit was greater in tetani than in twitches. The results indicate that the distribution of weak and strong inputs was not random, but that there was a tendency for one strong input to accompany a number of weak inputs (on average about two) on each muscle fibre. 7. Intracellular recording indicates that about 12% of fibres at 3-5 days may be electrically coupled. PMID:2824760

  5. Concentration of Non-Steroidal Anti-Inflammatory Drugs in the Pelvic Floor Muscles: An Experimental Comparative Rat Model

    PubMed Central

    Chin, Hung-Yen; Changchien, Eileen; Lin, Mei-Fung; Chiang, Chi-Hsin

    2014-01-01

    Purpose The aim of this study is to explore non-steroid anti-inflammation drugs (NSAIDs) potency for pelvic floor muscle pain by measuring local concentration in a rat model. Materials and Methods We used nine NSAIDs, including nabumetone, naproxen, ibuprofen, meloxicam, piroxicam, diclofenac potassium, etodolac, indomethacin, and sulindac, and 9 groups of female Wister rats. Each group of rats was fed with one kind of NSAID (2 mg/mL) for three consecutive days. Thereafter, one mL of blood and one gram of pelvic floor muscle were taken to measure drug pharmacokinetics, including partition coefficient, lipophilicity, elimination of half-life (T1/2) and muscle/plasma converting ratio (Css, muscle/Css, plasma). Results Diclofenac potassium had the lowest T1/2 and the highest mean Css, muscle/Css, plasma (1.9 hours and 0.85±0.53, respectively). The mean Css, muscle/Css, plasma of sulindac, naproxen and ibuprofen were lower than other experimental NSAIDs. Conclusion Diclofenac potassium had the highest disposition in pelvic floor muscle in a rat model. The finding implies that diclofenac potassium might be the choice for pain relief in pelvic muscle. PMID:24954342

  6. Epigallocatechin-3-gallate increases autophagy signaling in resting and unloaded plantaris muscles but selectively suppresses autophagy protein abundance in reloaded muscles of aged rats.

    PubMed

    Takahashi, Hideyuki; Suzuki, Yutaka; Mohamed, Junaith S; Gotoh, Takafumi; Pereira, Suzette L; Alway, Stephen E

    2017-03-07

    We have previously found that Epigallocatechin-3-gallate (EGCg), an abundant catechin in green tea, reduced apoptotic signaling and improved muscle recovery in response to reloading after hindlimb suspension (HS). In this study, we investigated if EGCg altered autophagy signaling in skeletal muscle of old rats in response to HS or reloading after HS. Fischer 344×Brown Norway inbred rats (age 34months) were given 1ml/day of purified EGCg (50mg/kg body weight), or the same sample volume of the vehicle by gavage. One group of animals received HS for 14days and the second group of rats received 14days of HS, then the HS was removed and they were allowed to recover by ambulating normally around the cage for two weeks. EGCg decreased a small number of autophagy genes in control muscles, but it increased the expression of other autophagy genes (e.g., ATG16L2, SNCA, TM9SF1, Pink1, PIM-2) and HS did not attenuate these increases. HS increased Beclin1, ATG7 and LC3-II/I protein abundance in hindlimb muscles. Relative to vehicle treatment, EGCg treatment had greater ATG12 protein abundance (35.8%, P<0.05), but decreased Beclin1 protein levels (-101.1%, P<0.05) after HS. However, in reloaded muscles, EGCg suppressed Beclin1 and LC3-II/I protein abundance as compared to vehicle treated muscles. EGCg appeared to "prime" autophagy signaling before and enhance autophagy gene expression and protein levels during unloading in muscles of aged rats, perhaps to improve the clearance of damaged organelles. However, EGCg suppressed autophagy signaling after reloading, potentially to increase the recovery of hindlimb muscles mass and function after loading is restored.

  7. Effects of fluvastatin and coenzyme Q10 on skeletal muscle in normo- and hypercholesterolaemic rats.

    PubMed

    Vincze, J; Jenes, Á; Füzi, M; Almássy, J; Németh, R; Szigeti, G; Dienes, B; Gaál, Z; Szentesi, P; Jóna, I; Kertai, P; Paragh, G; Csernoch, L

    2015-06-01

    Myalgia and muscle weakness may appreciably contribute to the poor adherence to statin therapy. Although the pathomechanism of statin-induced myopathy is not completely understood, changes in calcium homeostasis and reduced coenzyme Q10 levels are hypothesized to play important roles. In our experiments, fluvastatin and/or coenzyme Q10 was administered chronically to normocholesterolaemic or hypercholaestherolaemic rats, and the modifications of the calcium homeostasis and the strength of their muscles were investigated. While hypercholesterolaemia did not change the frequency of sparks, fluvastatin increased it on muscles both from normocholesterolaemic and from hypercholesterolaemic rats. This effect, however, was not mediated by a chronic modification of the ryanodine receptor as shown by the unchanged ryanodine binding in the latter group. While coenzyme Q10 supplementation significantly reduced the frequency of the spontaneous calcium release events, it did not affect their amplitude and spatial spread in muscles from fluvastatin-treated rats. This indicates that coenzyme Q10 supplementation prevented the spark frequency increasing effect of fluvastatin without having a major effect on the amount of calcium released during individual sparks. In conclusion, we have found that fluvastatin, independently of the cholesterol level in the blood, consistently and specifically increased the frequency of calcium sparks in skeletal muscle cells, an effect which could be prevented by the addition of coenzyme Q10 to the diet. These results support theories favouring the role of calcium handling in the pathophysiology of statin-induced myopathy and provide a possible pathway for the protective effect of coenzyme Q10 in statin treated patients symptomatic of this condition.

  8. Digital dissection of the masticatory muscles of the naked mole-rat, Heterocephalus glaber (Mammalia, Rodentia)

    PubMed Central

    Faulkes, Chris G.

    2014-01-01

    The naked mole-rat, Heterocephalus glaber, of the family Bathyergidae is a subterranean rodent that feeds on underground roots and tubers and digs extensive tunnel systems with its incisors. It is a highly unusual mammal with regard to its social structure, longevity, pain insensitivity and cancer resistance, all of which have made it the subject of a great deal of research in recent years. Yet, much of the basic anatomy of this species remains undocumented. In this paper, we describe the morphology of the jaw-closing musculature of the naked mole-rat, as revealed by contrast-enhanced micro-computed tomography. This technique uses an iodine stain to enable the imaging of soft tissues with microCT. The iodine-enhanced scans were used to create 3D reconstructions of the naked mole-rat masticatory muscles from which muscle masses were calculated. The jaw-closing musculature of Heterocephalus glaber is relatively very large compared to other rodents and is dominated by the superficial masseter, the deep masseter and the temporalis. The temporalis in particular is large for a rodent, covering the entirety of the braincase and much of the rear part of the orbit. The morphology of the masseter complex described here differs from two other published descriptions of bathyergid masticatory muscles, but is more similar to the arrangement seen in other rodent families. The zygomaticomandibularis (ZM) muscle does not protrude through the infraorbital foramen on to the rostrum and thus the naked mole-rat should be considered protrogomorphous rather than hystricomorphous, and the morphology is consistent with secondarily lost hystricomorphy as has been previously suggested for Bathyergidae. Overall, the morphology of the masticatory musculature indicates a species with a high bite force and a wide gape–both important adaptations for a life dominated by digging with the incisors. PMID:25024917

  9. Digital dissection of the masticatory muscles of the naked mole-rat, Heterocephalus glaber (Mammalia, Rodentia).

    PubMed

    Cox, Philip G; Faulkes, Chris G

    2014-01-01

    The naked mole-rat, Heterocephalus glaber, of the family Bathyergidae is a subterranean rodent that feeds on underground roots and tubers and digs extensive tunnel systems with its incisors. It is a highly unusual mammal with regard to its social structure, longevity, pain insensitivity and cancer resistance, all of which have made it the subject of a great deal of research in recent years. Yet, much of the basic anatomy of this species remains undocumented. In this paper, we describe the morphology of the jaw-closing musculature of the naked mole-rat, as revealed by contrast-enhanced micro-computed tomography. This technique uses an iodine stain to enable the imaging of soft tissues with microCT. The iodine-enhanced scans were used to create 3D reconstructions of the naked mole-rat masticatory muscles from which muscle masses were calculated. The jaw-closing musculature of Heterocephalus glaber is relatively very large compared to other rodents and is dominated by the superficial masseter, the deep masseter and the temporalis. The temporalis in particular is large for a rodent, covering the entirety of the braincase and much of the rear part of the orbit. The morphology of the masseter complex described here differs from two other published descriptions of bathyergid masticatory muscles, but is more similar to the arrangement seen in other rodent families. The zygomaticomandibularis (ZM) muscle does not protrude through the infraorbital foramen on to the rostrum and thus the naked mole-rat should be considered protrogomorphous rather than hystricomorphous, and the morphology is consistent with secondarily lost hystricomorphy as has been previously suggested for Bathyergidae. Overall, the morphology of the masticatory musculature indicates a species with a high bite force and a wide gape-both important adaptations for a life dominated by digging with the incisors.

  10. Transcriptome-wide RNA sequencing analysis of rat skeletal muscle feed arteries. I. Impact of obesity.

    PubMed

    Jenkins, Nathan T; Padilla, Jaume; Thorne, Pamela K; Martin, Jeffrey S; Rector, R Scott; Davis, J Wade; Laughlin, M Harold

    2014-04-15

    We employed next-generation RNA sequencing (RNA-Seq) technology to determine the influence of obesity on global gene expression in skeletal muscle feed arteries. Transcriptional profiles of the gastrocnemius and soleus muscle feed arteries (GFA and SFA, respectively) and aortic endothelial cell-enriched samples from obese Otsuka Long-Evans Tokushima Fatty (OLETF) and lean Long-Evans Tokushima Otsuka (LETO) rats were examined. Obesity produced 282 upregulated and 133 downregulated genes in SFA and 163 upregulated and 77 downregulated genes in GFA [false discovery rate (FDR) < 10%] with an overlap of 93 genes between the arteries. In LETO rats, there were 89 upregulated and 114 downregulated genes in the GFA compared with the SFA. There were 244 upregulated and 275 downregulated genes in OLETF rats (FDR < 10%) in the GFA compared with the SFA, with an overlap of 76 differentially expressed genes common to both LETO and OLETF rats in both the GFA and SFA. A total of 396 transcripts were found to be differentially expressed between LETO and OLETF in aortic endothelial cell-enriched samples. Overall, we found 1) the existence of heterogeneity in the transcriptional profile of the SFA and GFA within healthy LETO rats, 2) that this between-vessel heterogeneity was markedly exacerbated in the hyperphagic, obese OLETF rat, and 3) a greater number of genes whose expression was altered by obesity in the SFA compared with the GFA. Also, results indicate that in OLETF rats the GFA takes on a relatively more proatherogenic phenotype compared with the SFA.

  11. Role of Kv 4.3 in vibration-induced muscle pain in the rat

    PubMed Central

    Conner, Lindsay; Alvarez, Pedro; Bogen, Oliver; Levine, Jon D.

    2015-01-01

    We hypothesized that changes in the expression of Kv4.3 contribute to the mechanical hyperalgesia induced by vibration injury, a rodent model for hand-arm vibration syndrome in humans. Here we show that the exposure of the gastrocnemius muscle to vibration injury induces muscle hyperalgesia that is accompanied by a significant down-regulation of Kv4.3 in affected sensory nerve fibers in dorsal root ganglia (DRG). We additionally demonstrate that the intrathecal administration of antisense oligonucleotides for Kv4.3 mRNA itself induces muscle hyperalgesia in the rat. Our results suggest that attenuation in the expression of Kv4.3 may contribute to neuropathic pain in people affected by hand-arm vibration syndrome. PMID:26721612

  12. [Age-related excitability of the muscle after the sciatic nerve blockade in rats].

    PubMed

    Makiĭ, Ie A; Rodyns'kyĭ, O H; Tkachenko, V P

    2004-01-01

    In adult (8 weeks) and old (24 weeks) white rats early postdenervation changes (in 12 and 24 hours after nerves squeezing) of bioelectric activity of gastrocnemius muscles were studied using electrophysiological methods. Parameters of the activity were: a threshold, chronaxy during direct and indirect muscle irritation; amplitude, duration, the latent period of action potential (AP), an amplitude of AP during increasing stimulation and during dual irritations. It is established that the changes in these parameters in group of adult animals are considerably more pronounced and directed to the increase in excitability of the denervated muscle. In the group of old animals these changes were absent or they were considerably smaller. It is suggested that the cause of more pronounced postdenervated changes in adult animals is a higher speed of axoplasmic transport of the substances in the motor fibers of a isciatic nerve.

  13. Catalase-positive microperoxisomes in rat soleus and extensor digitorum longus muscle fiber types

    NASA Technical Reports Server (NTRS)

    Riley, Danny A.; Bain, James L. W.; Ellis, Stanley

    1988-01-01

    The size, distribution, and content of catalase-reactive microperoxisomes were investigated cytochemically in three types of muscle fibers from the soleus and the extensor digitorum longus (EDL) of male rats. Muscle fibers were classified on the basis of the mitochondrial content and distribution, the Z-band widths, and the size and shape of myofibrils as the slow-twitch oxidative (SO), the fast-twitch oxidative glycolytic (FOG), and the fast-twitch glycolytic (FG) fibers. It was found that both the EDL and soleus SO fibers possessed the largest microperoxisomes. A comparison of microperoxisome number per muscle fiber area or the microperoxisome area per fiber area revealed following ranking, starting from the largest number and the area-ratio values: soleus SO, EDL SO, EDL FOG, and EDL FG.

  14. Mechanisms of accelerated proteolysis in rat soleus muscle atrophy induced by unweighting or denervation

    NASA Technical Reports Server (NTRS)

    Tischler, Marc E.; Kirby, Christopher; Rosenberg, Sara; Tome, Margaret; Chase, Peter

    1991-01-01

    A hypothesis proposed by Tischler and coworkers (Henriksen et al., 1986; Tischler et al., 1990) concerning the mechanisms of atrophy induced by unweighting or denervation was tested using rat soleus muscle from animals subjected to hindlimb suspension and denervation of muscles. The procedure included (1) measuring protein degradation in isolated muscles and testing the effects of lysosome inhibitors, (2) analyzing the lysosome permeability and autophagocytosis, (3) testing the effects of altering calcium-dependent proteolysis, and (4) evaluating in vivo the effects of various agents to determine the physiological significance of the hypothesis. The results obtained suggest that there are major differences between the mechanisms of atrophies caused by unweighting and denervation, though slower protein synthesis is an important feature common for both.

  15. Effects of chronic centrifugation on skeletal muscle fibers in young developing rats

    NASA Technical Reports Server (NTRS)

    Martin, W. D.

    1980-01-01

    Three groups of 30-d old male and female rats were centrifuged for 2, 4, 8, and 16 weeks, after which their soleus and plantaris muscles were analysed for changes in proportions of muscle fiber types. The groups were: earth control, maintained at earth gravity without rotation; rotation control, subjected to a gravitational force of 1.05 G and 28 rpm; and rotation experimental, subjected to a gravitational force of 2 G and 28 rpm. Muscle fibers were classified into four fiber types on the basis of actomyosin ATPase activity as slow oxidative, fast oxidative glycolytic and either fast glycolytic (plantaris) or intermediate (soleus). Hypergravity resulted in an increase in slow oxidative fibers in soleus relative to the earth control, but not of females treated similarly. The relationship of body weight to the changes in proportion of slow oxidative fibers is discussed.

  16. Chronic sleep deprivation alters the myosin heavy chain isoforms in the masseter muscle in rats.

    PubMed

    Cao, Ruihua; Huang, Fei; Wang, Peihuan; Chen, Chen; Zhu, Guoxiong; Chen, Lei; Wu, Gaoyi

    2015-05-01

    To investigate the changes in myosin heavy chain (MyHC) isoforms of rat masseter muscle fibres caused by chronic sleep deprivation and a possible link with the pathogenesis of disorders of the temporomandibular joint (TMJ). A total of 180 male rats were randomly divided into three groups (n=60 in each): cage controls, large platform controls, and chronic sleep deprivation group. Each group was further divided into three subgroups with different observation periods (7, 14, and 21 days). We investigated he expression of MyHC isoforms in masseter muscle fibres by real-time quantitative polymerase chain reaction (PCR), Western blotting, and immunohistochemical staining. In rats with chronic sleep deprivation there was increased MyHC-I expression in layers of both shallow and deep muscles at 7 and 21 days compared with the control groups, whereas sleep deprivation was associated with significantly decreased MyHC-II expression. At 21 days, there were no differences in MyHC-I or MyHC-II expression between the groups and there were no differences between the two control groups at any time point. These findings suggest that chronic sleep deprivation alters the expression of MyHC isoforms, which may contribute to the pathogenesis of disorders of the TMJ.

  17. Age dependence of myosin heavy chain transitions induced by creatine depletion in rat skeletal muscle

    NASA Technical Reports Server (NTRS)

    Adams, Gregory R.; Baldwin, Kenneth M.

    1995-01-01

    This study was designed to test the hypothesis that myosin heavy chain (MHC) plasticity resulting from creatine depletion is an age-dependent process. At weaning (age 28 days), rat pups were placed on either standard rat chow (normal diet juvenile group) or the same chow supplemented with 1% wt/wt of the creatine analogue beta-guanidinopropionic acid (creatine depletion juvenile (CDJ) group). Two groups of adult rats (age approximately 8 wk) were placed on the same diet regimens (normal diet adult and creatine depletion adult (CDA) groups). After 40 days (CDJ and normal diet juvenile groups) and 60 days (CDA and normal diet adult groups), animals were killed and several skeletal muscles were removed for analysis of creatine content or MHC ditribution. In the CDJ group, creatine depletion (78%) was accompanied by significant shifts toward expression of slower MHC isoforms in two slow and three fast skeletal muscles. In contrast, creatine depletion in adult animals did not result in similar shifts toward slow MHC isoform expression in either muscle type. The results of this study indicate that there is a differential effect of creatine depletion on MHC tranitions that appears to be age dependent. These results strongly suggest that investigators contemplating experimental designs involving the use of the creatine analogue beta-guanidinopropionic acid should consider the age of the animals to be used.

  18. A novel signalling pathway originating in mitochondria modulates rat skeletal muscle membrane excitability

    PubMed Central

    Ørtenblad, Niels; Stephenson, D George

    2003-01-01

    Single skeletal muscle fibres from rat and cane toad were mechanically skinned and stimulated either electrically by initiating action potentials in the sealed transverse (t-) tubular system or by ion substitution causing depolarisation of the t-system to pre-determined levels. Depression of mitochondrial ATP-producing function with three diverse mitochondrial function antagonists (azide: 1–10 mm; oligomycin 1 μg ml−1 and carbonyl cyanide 4-trifluoromethoxyphenylhydrazone (FCCP) 1 μm), under conditions in which the cytosolic ATP was maintained high and constant, invariably reduced the excitability of rat fibres but had no obvious effect on the excitability of toad fibres, where mitochondria are less abundant and differently located. The reduction in excitability linked to mitochondria in rat fibres appears to be caused by depolarisation of the sealed t-system membrane. These observations suggest that mitochondria can regulate the functional state of mammalian muscle cells and have important implications for understanding how the balance between ATP utilisation and ATP production is regulated at the cellular level in general and in mammalian skeletal muscle fibres in particular. PMID:12611917

  19. Voltage-dependent effects of barnidipine in rat vascular smooth muscle.

    PubMed

    Wegener, J W; Korstanje, C; Nawrath, H

    2003-08-01

    The effects of the dihydropyridine nifedipine and its more lipophilic congener, barnidipine, were investigated in smooth muscle preparations from the rat in resting and depolarizing conditions. Both drugs relaxed precontracted aortic rings more potently in depolarizing conditions, barnidipine being more potent than nifedipine. Currents through Ca2+ channels in rat vascular smooth muscle cells (A7r5) and in isolated rat cardiomyocytes were reduced more potently by both drugs at a holding potential of -40 mV than at -80 mV. However, barnidipine and nifedipine were more effective in reducing the current in A7r5 cells than in cardiomyocytes. The IC(50) obtained in aortic rings and in A7r5 cells were similar for barnidipine but an order of magnitude different for nifedipine. The results show that, in depolarizing conditions, barnidipine was more effective than nifedipine. It is suggested that the higher potency of barnidipine acting in vascular smooth muscle is related to both a higher affinity to the inactivated state of vascular Ca2+ channels and to a more lipophilic property as compared with nifedipine.

  20. Lymphatic Muscle Cells in Rat Mesenteric Lymphatic Vessels of Various Ages

    PubMed Central

    Bridenbaugh, Eric A.; Nizamutdinova, Irina Tsoy; Jupiter, Daniel; Nagai, Takashi; Thangaswamy, Sangeetha; Chatterjee, Victor

    2013-01-01

    Abstract Background Recent studies on aging-associated changes in mesenteric lymph flow in situ demonstrated predominance of the severe negative chronotropic effect of aging on the contractility of aged mesenteric lymphatic vessels (MLV). At the same time, contraction amplitude of the aged vessels was only slightly diminished by aging and can be rapidly stimulated within 5–15 minutes. However, the detailed quantitative evaluation of potential aging-associated changes in muscle cells investiture in MLV has never been performed. Methods and Results In this study we, for the first time, performed detailed evaluation of muscle cells investiture in MLV in reference to the position of lymphatic valve in different zones of lymphangion within various age groups (3-mo, 9-mo and 24-mo Fischer-344 rats). Using visual and quantitative analyses of the images of MLV immunohistochemically labeled for actin, we confirmed that the zones located close upstream (pre-valve zones) and above lymphatic valves (valve zones) possess the lowest investiture of lymphatic muscle cells. Most of the high muscle cells investiture zones exist downstream to the lymphatic valve (post-valve zones). The muscle cells investiture of these zones is not affected by aging, while pre-valve and valve zones demonstrate significant aging-associated decrease in muscle cells investiture. Conclusions The low muscle cells investiture zones in lymphatic vessels consist of predominantly longitudinally oriented muscle cells which are positioned in pre-valve and valve zones and connect adjacent lymphangions. These cells may provide important functional impact on the biomechanics of the lymphatic valve gating and electrical coupling between lymphangions, while their aging-associated changes may delimit adaptive reserves of aged lymphatic vessels. PMID:23531183

  1. Expression of calcium-buffering proteins in rat intrinsic laryngeal muscles.

    PubMed

    Ferretti, Renato; Marques, Maria Julia; Khurana, Tejvir S; Santo Neto, Humberto

    2015-06-01

    Intrinsic laryngeal muscles (ILM) are highly specialized muscles involved in phonation and airway protection, with unique properties that allow them to perform extremely rapid contractions and to escape from damage in muscle dystrophy. Due to that, they may differ from limb muscles in several physiological aspects. Because a better ability to handle intracellular calcium has been suggested to explain ILM unique properties, we hypothesized that the profile of the proteins that regulate calcium levels in ILM is different from that in a limb muscle. Calcium-related proteins were analyzed in the ILM, cricothyroid (CT), and tibialis anterior (TA) muscles from male Sprague-Dawley rats (8 weeks of age) using quantitative PCR and western blotting. Higher expression of key Ca(2+) regulatory proteins was detected in ILM compared to TA, such as the sarcoplasmic reticulum (SR) Ca(2+)-reuptake proteins (Sercas 1 and 2), the Na(+)/Ca(2+) exchanger, phospholamban, and the Ca(2+)-binding protein calsequestrin. Parvalbumin, calmodulin and the ATPase, Ca(2+)-transporting, and plasma membrane 1 were also expressed at higher levels in ILM compared to TA. The store-operated calcium entry channel molecule was decreased in ILM compared to the limb muscle and the voltage-dependent L-type and ryanodine receptor were expressed at similar levels in ILM and TA. These results show that ILM have a calcium regulation system profile suggestive of a better ability to handle calcium changes in comparison to limb muscles, and this may provide a mechanistic insight for their unique pathophysiological properties.

  2. Expression of calcium-buffering proteins in rat intrinsic laryngeal muscles

    PubMed Central

    Ferretti, Renato; Marques, Maria Julia; Khurana, Tejvir S; Santo Neto, Humberto

    2015-01-01

    Intrinsic laryngeal muscles (ILM) are highly specialized muscles involved in phonation and airway protection, with unique properties that allow them to perform extremely rapid contractions and to escape from damage in muscle dystrophy. Due to that, they may differ from limb muscles in several physiological aspects. Because a better ability to handle intracellular calcium has been suggested to explain ILM unique properties, we hypothesized that the profile of the proteins that regulate calcium levels in ILM is different from that in a limb muscle. Calcium-related proteins were analyzed in the ILM, cricothyroid (CT), and tibialis anterior (TA) muscles from male Sprague–Dawley rats (8 weeks of age) using quantitative PCR and western blotting. Higher expression of key Ca2+ regulatory proteins was detected in ILM compared to TA, such as the sarcoplasmic reticulum (SR) Ca2+-reuptake proteins (Sercas 1 and 2), the Na+/Ca2+ exchanger, phospholamban, and the Ca2+-binding protein calsequestrin. Parvalbumin, calmodulin and the ATPase, Ca2+-transporting, and plasma membrane 1 were also expressed at higher levels in ILM compared to TA. The store-operated calcium entry channel molecule was decreased in ILM compared to the limb muscle and the voltage-dependent L-type and ryanodine receptor were expressed at similar levels in ILM and TA. These results show that ILM have a calcium regulation system profile suggestive of a better ability to handle calcium changes in comparison to limb muscles, and this may provide a mechanistic insight for their unique pathophysiological properties. PMID:26109185

  3. Sarcomere length and capillary curvature of rat hindlimb muscles in vivo.

    PubMed

    Ledvina, M A; Segal, S S

    1995-06-01

    Mammalian skeletal muscle fibers have been reported to develop maximum force at a sarcomere length (Ls) of approximately 2.5 microns. However, the functional range of muscle length (Lm) and Ls encountered by skeletal muscle in vivo is not well defined. Changes in Ls markedly influence capillary geometry, but this effect has been shown only in fixed preparations. The purpose of this study was to evaluate the influence of limb position on Lm, Ls, and capillary geometry in living undisturbed hindlimb muscles. We tested the hypothesis that maximal excursion of the foot would have similar effects on Ls and capillary geometry of antagonistic soleus (Sol) and extensor digitorum longus (EDL) muscles in vivo. Female Sprague-Dawley rats (n = 9; 243 +/- 3 g) were anesthetized (pentobarbital sodium; 35 mg/kg). The right Sol and EDL muscles were exposed and irrigated with physiological saline solution (34 degrees C; pH 7.4). Sarcomeres and capillaries were observed with video microscopy (total magnification x 1,900; spatial resolution < 1 micron); sarcomeres were labeled with a fluorescent dye [4-(4-diethylaminostyryl)-N-methylpyridinium iodide]. As foot angle increased from 30 degrees (maximal dorsiflexion) to 170 degrees (maximal plantarflexion), Lm and Ls increased for EDL muscles (27.51 +/- 0.42 to 30.97 +/- 0.25 mm and 2.33 +/- 0.01 to 3.09 +/- 0.05 microns, respectively; P < 0.05) and decreased for Sol muscles (26.09 +/- 0.38 to 20.27 +/- 0.34 mm and 3.17 +/- 0.03 to 2.22 +/- 0.04 microns, respectively; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Calpain 3 Expression Pattern during Gastrocnemius Muscle Atrophy and Regeneration Following Sciatic Nerve Injury in Rats

    PubMed Central

    Wu, Ronghua; Yan, Yingying; Yao, Jian; Liu, Yan; Zhao, Jianmei; Liu, Mei

    2015-01-01

    Calpain 3 (CAPN3), also known as p94, is a skeletal muscle-specific member of the calpain family that is involved in muscular dystrophy; however, the roles of CAPN3 in muscular atrophy and regeneration are yet to be understood. In the present study, we attempted to explain the effect of CAPN3 in muscle atrophy by evaluating CAPN3 expression in rat gastrocnemius muscle following reversible sciatic nerve injury. After nerve injury, the wet weight ratio and cross sectional area (CSA) of gastrocnemius muscle were decreased gradually from 1–14 days and then recovery from 14–28 days. The active form of CAPN3 (~62 kDa) protein decreased slightly on day 3 and then increased from day 7 to 14 before a decrease from day 14 to 28. The result of linear correlation analysis showed that expression of the active CAPN3 protein level was negatively correlated with muscle wet weight ratio. CAPN3 knockdown by short interfering RNA (siRNA) injection improved muscle recovery on days 7 and 14 after injury as compared to that observed with control siRNA treatment. Depletion of CAPN3 gene expression could promote myoblast differentiation in L6 cells. Based on these findings, we conclude that the expression pattern of the active CAPN3 protein is linked to muscle atrophy and regeneration following denervation: its upregulation during early stages may promote satellite cell renewal by inhibiting differentiation, whereas in later stages, CAPN3 expression may be downregulated to stimulate myogenic differentiation and enhance recovery. These results provide a novel mechanistic insight into the role of CAPN3 protein in muscle regeneration after peripheral nerve injury. PMID:26569227

  5. Differential effects of endurance training and creatine depletion on regional mitochondrial adaptations in rat skeletal muscle.

    PubMed Central

    Roussel, D; Lhenry, F; Ecochard, L; Sempore, B; Rouanet, J L; Favier, R

    2000-01-01

    To examine the combined effects of 2-week endurance training and 3-week feeding with beta-guanidinopropionic acid (GPA) on regional adaptability of skeletal muscle mitochondria, intermyofibrillar mitochondria (IFM) and subsarcolemmal mitochondria (SSM) were isolated from quadriceps muscles of sedentary control, trained control, sedentary GPA-fed and trained GPA-fed rats. Mitochondrial oxidative phosphorylation was assessed polarographically by using pyruvate plus malate, succinate (plus rotenone), and ascorbate plus N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) (plus antimycin) as respiratory substrates. Assays of cytochrome c oxidase and F(1)-ATPase activities were also performed. In sedentary control rats, IFM exhibited a higher oxidative capacity than SSM, whereas F(1)-ATPase activities were similar. Training increased the oxidative phosphorylation capacity of mitochondria with both pyruvate plus malate and ascorbate plus TMPD as substrates, with no differences between IFM and SSM. In contrast, the GPA diet mainly improved the overall SSM oxidative phosphorylation capacity, irrespective of the substrate used. Finally, the superimposition of training to feeding with GPA strongly increased both oxidase and enzymic activities in SSM, whereas no cumulative effects were found in IFM mitochondria. It therefore seems that endurance training and feeding with GPA, which are both known to alter the energetic status of the muscle cell, might mediate distinct biochemical adaptations in regional skeletal muscle mitochondria. PMID:10947970

  6. Proteome-wide muscle protein fractional synthesis rates predict muscle mass gain in response to a selective androgen receptor modulator in rats.

    PubMed

    Shankaran, Mahalakshmi; Shearer, Todd W; Stimpson, Stephen A; Turner, Scott M; King, Chelsea; Wong, Po-Yin Anne; Shen, Ying; Turnbull, Philip S; Kramer, Fritz; Clifton, Lisa; Russell, Alan; Hellerstein, Marc K; Evans, William J

    2016-03-15

    Biomarkers of muscle protein synthesis rate could provide early data demonstrating anabolic efficacy for treating muscle-wasting conditions. Androgenic therapies have been shown to increase muscle mass primarily by increasing the rate of muscle protein synthesis. We hypothesized that the synthesis rate of large numbers of individual muscle proteins could serve as early response biomarkers and potentially treatment-specific signaling for predicting the effect of anabolic treatments on muscle mass. Utilizing selective androgen receptor modulator (SARM) treatment in the ovariectomized (OVX) rat, we applied an unbiased, dynamic proteomics approach to measure the fractional synthesis rates (FSR) of 167-201 individual skeletal muscle proteins in triceps, EDL, and soleus. OVX rats treated with a SARM molecule (GSK212A at 0.1, 0.3, or 1 mg/kg) for 10 or 28 days showed significant, dose-related increases in body weight, lean body mass, and individual triceps but not EDL or soleus weights. Thirty-four out of the 94 proteins measured from the triceps of all rats exhibited a significant, dose-related increase in FSR after 10 days of SARM treatment. For several cytoplasmic proteins, including carbonic anhydrase 3, creatine kinase M-type (CK-M), pyruvate kinase, and aldolase-A, a change in 10-day FSR was strongly correlated (r(2) = 0.90-0.99) to the 28-day change in lean body mass and triceps weight gains, suggesting a noninvasive measurement of SARM effects. In summary, FSR of multiple muscle proteins measured by dynamics of moderate- to high-abundance proteins provides early biomarkers of the anabolic response of skeletal muscle to SARM.

  7. Adrenergic denervation hypersensitivity in ileal circular smooth muscle after small bowel transplantation in rats.

    PubMed

    Shibata, C; Balsiger, B M; Anding, W J; Sarr, M G

    1997-11-01

    Effects of small bowel transplantation (SBT) on ileal motility are unknown. The aim of the present study was to investigate changes in spontaneous contractile activity and sensitivity to cholinergic and adrenergic agents in the ileal circular muscle after SBT in rats. Orthotopic SBT was performed in syngeneic rats to avoid immune phenomena. Distal ileal circular muscle strips from rats one week (N = 10) and eight weeks (N = 10) after SBT were stretched to optimal length (Lo), and basal spontaneous activity at Lo was measured. Dose-response experiments to the cholinergic agonist bethanechol (Be, 10(-8)-10(-4) M) were performed in the presence of tetrodotoxin (TTX, 10(-6) M) and to the adrenergic agonist norepinephrine (NE, 10(-8)-10(-4) M) with or without TTX. ED50 (negative log of drug-concentration that induced 50% effect) was calculated. We also studied rats with selective jejunoileal ischemia/ reperfusion, intestinal transection/reanastomosis, naive controls, and sham operated controls (N > or = 8/group). Spontaneous basal activity did not differ among groups. Sensitivity to Be was not different in rats after SBT or in other groups compared to control tissue. After SBT, hypersensitivity to NE was shown by a significant increase of ED50 at one and eight weeks after SBT (5.1 +/- 0.3 vs 6.2 +/- 0.4 and 6.2 +/- 0.2, respectively; P < 0.05) regardless of the presence of TTX. No hypersensitivity was observed after ischemia-reperfusion intestinal transection-reanastomosis, or sham operation. It is concluded that ileal hypersensitivity to NE was related to the extrinsic denervation obligated by the transplantation procedure, possibly mediated through an increase in number of receptors on smooth muscle, not on the enteric nerves.

  8. The labile respiratory activity of ribcage muscles of the rat during sleep.

    PubMed

    Megirian, D; Pollard, M J; Sherrey, J H

    1987-08-01

    1. Sleep-waking states of chronically implanted rats were identified polygraphically while recording the integrated electromyogram (e.m.g.) of extrinsic (scalenus medius and levator costae) and intrinsic (external and internal interosseous intercostal and parasternal) muscles of the thoracic cage. Rats breathed air, air enriched in CO2 (5%) or air deficient in O2 (10% O2 in N2) and were free to adopt any desired posture. 2. In non-rapid eye movement (non-r.e.m.) sleep, the scalenus medius and intercostal muscles of the cephalic spaces were always inspiratory; intercostal muscles of the mid-thoracic spaces were commonly expiratory while the more caudal ones were only occasionally expiratory. Expiratory activity, when present in quiet wakefulness, extended for a variable period of time into non-r.e.m. sleep and always disappeared in r.e.m. sleep regardless of the ribcage muscle under study. 3. Inspiratory activity, when present in non-r.e.m. sleep, was unaffected, partially attenuated or abolished at entry into r.e.m. sleep. The peak integrated e.m.g. activity of ribcage muscles was measured as a function of posture, gas mixture breathed and ribcage site: (a) the greater the degree of curled-up posture, the greater the respiratory activity of scalenus medius, an effect augmented by CO2 but depressed by hypoxia, and (b) the more caudally placed ribcage muscles exhibited respiratory activity which was essentially unaffected by posture and gas mixture inspired. 4. The presence or absence of tonic activity in ribcage respiratory muscles during non-r.e.m. sleep was unrelated to posture. When tonic activity was present, it always disappeared in r.e.m. sleep. When expiratory activity was present in non-r.e.m. sleep, it too always disappeared in r.e.m. sleep. Inspiratory activity present in non-r.e.m. sleep was variably affected at entry into r.e.m. sleep; it was unchanged, partially attenuated or abolished. 5. It is concluded that thoracic cage muscles exhibit marked

  9. [Ultrastructure of the blood vessels and muscle fibers in the skeletal muscle of rats flown on the Kosmos-605 and Kosmos-782 biosatellites].

    PubMed

    Savik, Z F; Rokhlenko, K D

    1981-01-01

    Electron microscopy was used to study ultrastructures of the wall of blood vessels and muscle fibers of the red (soleus) and mixed (gastrocnemius) muscles of rats flown on Cosmos-605 for 22.5 days and on Cosmos-782 for 19,5 days and sacrificed 4-6 hours, 48 hours and 25-27 days postflight. It was demonstrated that the orbital flight did not induce significant changes in the ultrastructure of blood vessels of the soleus and gastrocnemius muscles but caused atrophy of muscle fibers and reduction of the number of functioning capillaries. Readaptation of the soleus vascular system to 1 g led to degradation of permeability of capillary and venular walls and development of edema of the perivascular connective tissue. This may be one of the factors responsible for dystrophic changes in muscle fibers.

  10. Microvascular responses to body tilt in cutaneous maximus muscle of conscious rats

    NASA Technical Reports Server (NTRS)

    Puri, Rohit K.; Segal, Steven S.

    1994-01-01

    We investigated microvascular responses to head-up tilt (HUT) and head-down tilt (HDT) in striated muscle of conscious male rats. To observe the microcirculation in the cutaneous maximus muscle, a transparent polycarbonate chamber was implanted aseptically into a skin fold created between the shoulders. Rats were trained to sit quietly during HUT and HDT while positioned on a horizontal microscope that rotated in the sagittal plane. At 4-5 days after surgery, arteriole and venule diameters were recorded using videomicroscopy while the rat experienced 10 min each (in random order) of HUT or HDT at 20 deg or 40 deg separated by 2-h rest periods. HUT had no affect on microvessel diameter; 20 deg HDT had little affect. In response to 40 deg HDT, 'large' arterioles constricted by 18 +/- 2% and 'small' arterioles dilated by 21 +/- 3%; this difference suggested variation in mechanisms controlling arteriolar responses. Venules exhibited a larger fluctuation in diameter during 40 deg HDT compared with other body positions, suggesting that venomotor activity may be induced with sufficient fluid shift or change in central venous pressure. These observations illustrate a viable model for studying microvascular responses to gravitational stress in conscious rats.

  11. Evaluation of iron bioavailability from bonito dark muscle using anemic rats.

    PubMed

    Matsumoto, Junichi; Mori, Nahomi; Doi, Mikiharu; Kishida, Taro; Ebihara, Kiyoshi

    2003-07-16

    The bioavailability of iron from ferrous sulfate (FeII-S), heme iron prepared from hemoglobin (HIP), and bonito dark muscle (BDM) was assessed in anemic rats using a hemoglobin regeneration efficiency (HRE) method. Freeze-dried BDM (FD), boiled and freeze-dried BDM (B/FD), and boiled and smoke-dried BDM (B/SD) were used as BDM source. Rats were made anemic by feeding on an iron-deficient diet for 28 days. To replete their iron levels, anemic rats were then fed on a diet containing iron at a level of 17 ppm for 14 days. Rats receiving FeII-S gained significantly more weight and had greater food intake and higher HRE compared to the other four groups. The bioavailability of iron from HIP was poor compared with that from FeII-S and BDM. When the HRE of rats fed FeII-S was 100, that of rats fed BDF was approximately 80. These results suggest that BMD is an effective dietary source of iron.

  12. Histochemical localization of rhodanese activity in rat liver and skeletal muscle.

    PubMed

    Devlin, D J; Mills, J W; Smith, R P

    1989-02-01

    A previously described histochemical technique was applied to the localization of rhodanese (thiosulfate sulfurtransferase, EC 2.8.1.1) activity in rat skeletal muscle and liver. The physiological function of rhodanese is controversial, but it and other sulfurtransferases can catalyze the conversion of cyanide to the much less toxic thiocyanate. The volume of distribution of cyanide in human and dog is said to correspond roughly to the blood volume. Because of this and other observations, it was hypothesized that sulfurtransferase activity associated with the vascular endothelium on smooth muscle layers of blood vessels might play a role in cyanide detoxification. However, little enzyme activity as identified histochemically was associated with those sites in comparison with others examined. As expected, high activity was found in the liver and moderately high levels were present in skeletal muscle. In muscles sectioned longitudinally, points of rhodanese staining occurred in linear arrays along the lengths of the muscle fiber corresponding to the location of mitochondria within the fiber. The original technique called for incubation of tissue sections with both thiosulfate and cyanide. When thiosulfate was omitted, staining for rhodanese activity was still clearly identifiable in both liver and muscle sections with cyanide alone. In muscle sections the inclusion of both thiosulfate and cyanide resulted in a preferential staining of type I fibers presumably because of their higher content of mitochondria. Thus, this technique is a potential alternative to the NADH dehydrogenase stain for distinguishing between type I and type II muscle fibers. Incubation of tissue sections with only thiosulfate produced results that did not appear to differ from those obtained when both substrates were omitted. From these observations it may be inferred that the endogenous pool of sulfane-sulfur available to sulfurtransferases is larger than any alleged endogenous pool of cyanide

  13. Effects of low level laser in the morphology of the skeletal muscle fiber during compensatory hypertrophy in plantar muscle of rats

    NASA Astrophysics Data System (ADS)

    Terena, Stella Maris Lins; Fernandes, Kristianne Porta Santos; Kalil, Sandra; Alves, Agnelo Neves; Mesquita Ferrari, Raquel Agnelli

    2015-06-01

    The hypertrophy is known as an increase the cross-sectional area of the muscle as a result of a muscular work against an overload, and it is compensatory because the overload is induced by functional elimination of synergistic muscles. The importance of study the compensatory hypertrophy is understand how this process can be influenced by the irradiation with regard to the weight and muscle cross-sectional area, to assist in the rehabilitation process and the effectiveness functional return. The aim was evaluate the effects of low-level laser irradiation on morphological aspects of muscle tissue, comparing the weight and cross-sectional area in rat skeletal muscle. Wistar rats were divided into three groups: control, hypertrophy group without irradiation (right plantar muscle) and hypertrophy group and irradiation (left plantar muscle), both analyzed after 7 and 14 days. The irradiation was performed daily immediately after the surgery. The parameters were: λ = 780nm, beam spot of 0.04 cm2, output power of 40mW, power density of 1W/cm2, energy density of 10J / cm2 and 10s exposure time with a total energy of 3.2 J. The results revealed that low level laser irradiation an increase the weight of the plantaris muscle after 7 and 14 days with a difference of 7.06% and 11.51% respectively. In conclusion, low level laser irradiation has an effect on compensatory hypertrophy to produce increased muscle weight and promoted an increase in cross-sectional area of muscle fibers in the compensatory hypertrophy model after 14 days with parameters cited above.

  14. Carnitine supplementation to obese Zucker rats prevents obesity-induced type II to type I muscle fiber transition and favors an oxidative phenotype of skeletal muscle

    PubMed Central

    2013-01-01

    Background In the present study, we tested the hypothesis that carnitine supplementation counteracts obesity-induced muscle fiber transition from type I to type II. Methods 24 obese Zucker rats were randomly divided into two groups of 12 rats each (obese control, obese carnitine) and 12 lean Zucker rats were selected for lean control group. A control diet was given to both control groups and a carnitine supplemented diet (3 g/kg diet) was given to obese carnitine group for 4 wk. Components of the muscle fiber transformation in skeletal muscle were examined. Results The plasma level of carnitine were lower in the obese control group compared to the lean control group and higher in the obese carnitine group than in the other groups (P < 0.05). Plasma concentrations of triglycerides and non-esterified fatty acids were increased in obese animals compared to lean animals and the obese carnitine group had lower level compared to the obese control group (P < 0.05). The obese carnitine group had an increased number of type I muscle fibers and higher mRNA levels of type I fiber-specific myosin heavy chain, regulators of muscle fiber transition and of genes involved in carnitine uptake, fatty acid transport, β-oxidation, angiogenesis, tricarboxylic acid cycle and thermo genesis in M. rectus femoris compared to the other groups (P < 0.05). Conclusion The results demonstrate that carnitine supplementation to obese Zucker a rat counteracts the obesity-induced muscle fiber transition and restores the muscle oxidative metabolic phenotype. Carnitine supplementation is supposed to be beneficial for the treatment of elevated levels of plasma lipids during obesity or diabetes. PMID:23842456

  15. Chronic stress effects in contralateral medial pterygoid muscle of rats with occlusion alteration.

    PubMed

    Loyola, Bruno Melo; Nascimento, Glauce Crivelaro; Fernández, Rodrigo Alberto Restrepo; Iyomasa, Daniela Mizusaki; Pereira, Yamba Carla Lara; Leite-Panissi, Christie Ramos Andrade; Issa, João Paulo Mardegan; Iyomasa, Mamie Mizusaki

    2016-10-01

    Temporomandibular disorder (TMD) has a high prevalence in our society, characterized by a severe pain condition of the masticatory muscles and temporomandibular joint. Despite the indication of multiple factor initiators of TMD, there is still controversy about its etiology and its pathophysiology is poorly understood. Using rats as experimental animals we investigated the effect of unpredictable chronic stress with or without unilateral molar extraction on the contralateral medial pterygoid muscle. Our hypothesis is that these two factors induce changes in morphology, oxidative metabolism and oxidative stress of muscle fibers. Young adult male Wistar rats (±200g) were divided into four groups: a group with extraction and unpredictable chronic stress (E+US); with extraction and without stress (E+C); without extraction and with unpredictable chronic stress (NO+US); and a control group without either extraction or stress (NO+C). The animals were subjected to unilateral extraction of the upper left molars, under intraperitoneal anesthesia with 4% Xylazine (10mg/kg) and 10% Ketamine (80mg/kg) on day zero. The rats of groups E+US and NO+US were submitted to different protocols of stress, from the 14th day after the extraction. The protocols were different every day for five consecutive days, which were repeated from the 6th day for five days more. Contralateral medial pterygoid muscles were obtained on the 24th day after the start of the experiment for morphological, metabolic, capillary density, and oxidative stress analysis. The data from capillary density showed a decrease of capillaries in animals subjected to dental extraction, compared with those without extraction and an increase of laminin expression in the group submitted to the unpredictable chronic stress when compared to the unexposed to stress. SDH test revealed a decrease of light fibers in the group submitted to unilateral extraction of molars, compared with this area in the control group. In E+US and NO

  16. Morphological and biochemical changes in soleus and extensor digitorum longus muscles of rats orbited in Spacelab 3

    NASA Technical Reports Server (NTRS)

    Riley, D. A.; Slocum, T.; Bain, J. L. W.; Sedlak, F. R.; Elis, S.; Satyanarayana, T.

    1985-01-01

    Muscle atrophy in rats exposed to hypogravity for seven days aboard Spacelab 3 is examined. Hindlimb muscles were harvested 12-16 days postflight, and prepared for enzyme studies and electron microscopy. Simple cell shrinkage was found, with a mean fiber area decrease of 35.8 percent for soleus and 24.9 percent for extensor digitorum longus (EDL) flight muscle fibers, as compared with control muscle fibers. EDL and soleus muscles showed increases in alkaline myofibrillar ATPase, alpha glycerophosphate dehydrogenase, and glycogen, and a decrease in NADH dehydrogenase staining. The 26 percent increase in calcium activated protease suggests that the focal degradation of myofibrils is the key process of myofibril breakdown. The presence in the flight soleus muscles of one percent necrotic fibers is unexplained. The observed shift towards histochemical fast-muscle type properties is consistent with previous findings.

  17. Spaceflight on STS-48 and earth-based unweighting produce similar effects on skeletal muscle of young rats

    NASA Technical Reports Server (NTRS)

    Tischler, Marc E.; Henriksen, Erik J.; Munoz, Kathryn A.; Stump, Craig S.; Woodman, Christopher R.; Kirby, Christopher R.

    1993-01-01

    Eight female albino rats were exposed to 5.4 days of weightlessness aboard the Space Shuttle mission STS-48 in 1991. An asynchronous ground control experiment mimicked the flight cage conditions and mission duration of the STS-48 rats, and a third group of animals underwent limb suspension for 5.4 days. The flight animals gained a greater percentage of body mass per day despite similar rates of food consumption in the three groups. The results obtained on insulin response and muscle size show that a tail-cast hindlimb-suspension model is suitable for mimicking the effects of weightlessness on rapidly growing juvenile rat muscles.

  18. Effect of ethyl pyruvate on skeletal muscle metabolism in rats fed on a high fat diet.

    PubMed

    Olek, Robert A; Ziolkowski, Wieslaw; Wierzba, Tomasz H; Kaczor, Jan J

    2013-07-01

    Impaired mitochondrial capacity may be implicated in the pathology of chronic metabolic diseases. To elucidate the effect of ethyl pyruvate supplementation on skeletal muscles metabolism we examined changes in activities of mitochondrial and antioxidant enzymes, as well as sulfhydryl groups oxidation (an indirect marker of oxidative stress) during the development of obesity. After 6 weeks feeding of control or high fat diet, Wistar rats were divided into four groups: control diet, control diet and ethyl pyruvate, high fat diet, and high fat diet and ethyl pyruvate. Ethyl pyruvate was administered as 0.3% solution in drinking water, for the following 6 weeks. High fat diet feeding induced the increase of activities 3-hydroxyacylCoA dehydrogenase, citrate synthase, and fumarase. Moreover, higher catalase and superoxide dismutase activities, as well as sulfhydryl groups oxidation, were noted. Ethyl pyruvate supplementation did not affect the mitochondrial enzymes' activities, but induced superoxide dismutase activity and sulfhydryl groups oxidation. All of the changes were observed in soleus muscle, but not in extensor digitorum longus muscle. Additionally, positive correlations between fasting blood insulin concentration and activities of catalase (p = 0.04), and superoxide dismutase (p = 0.01) in soleus muscle were noticed. Prolonged ethyl pyruvate consumption elevated insulin concentration, which may cause modifications in oxidative type skeletal muscles.

  19. Overexpression of SIRT1 in Rat Skeletal Muscle Does Not Alter Glucose Induced Insulin Resistance

    PubMed Central

    Brandon, Amanda E.; Tid-Ang, Jennifer; Wright, Lauren E.; Stuart, Ella; Suryana, Eurwin; Bentley, Nicholas; Turner, Nigel; Cooney, Gregory J.; Ruderman, Neil B.; Kraegen, Edward W.

    2015-01-01

    SIRT1 is a NAD+-dependent deacetylase thought to regulate cellular metabolic pathways in response to alterations in nutrient flux. In the current study we investigated whether acute changes in SIRT1 expression affect markers of muscle mitochondrial content and also determined whether SIRT1 influenced muscle insulin resistance induced by acute glucose oversupply. In male Wistar rats either SIRT1 or a deacetylase inactive mutant form (H363Y) was electroprated into the tibialis cranialis (TC) muscle. The other leg was electroporated with an empty control vector. One week later, glucose was infused and hyperglycaemia was maintained at ~11mM. After 5 hours, 11mM glucose induced significant insulin resistance in skeletal muscle. Interestingly, overexpression of either SIRT1 or SIRT1 (H363Y) for 1 week did not change markers of mitochondrial content or function. SIRT1 or SIRT1 (H363Y) overexpression had no effect on the reduction in glucose uptake and glycogen synthesis in muscle in response to hyperglycemia. Therefore we conclude that acute increases in SIRT1 protein have little impact on mitochondrial content and that overexpressing SIRT1 does not prevent the development of insulin resistance during hyperglycaemia. PMID:25798922

  20. Extracellular hyperosmotic stress stimulates glucose uptake in incubated fast-twitch rat skeletal muscle.

    PubMed

    Farlinger, Chris M; Lui, Adrian J; Harrison, Rose C; LeBlanc, Paul J; Peters, Sandra J; Roy, Brian D

    2013-06-01

    The influence of hyperosmotic stress on glucose uptake, handling, and signaling processes remains unclear in mammalian skeletal muscle. Thus, the purpose of this study was to investigate alterations in glucose uptake and handling during extracellular hyperosmotic stress in isolated fast-twitch mammalian skeletal muscle. Using an established in vitro isolated whole-muscle model, extensor digitorum longus (EDL) muscles were dissected from male rats (4-6 weeks of age) and incubated (30-60 min) in an organ bath, containing Sigma Medium-199 with 8 mmol·L(-1) D-glucose, and mannitol was added to the targeted osmolalities (ISO, iso-osmotic, 290 mmol·kg(-1); HYPER, hyperosmotic, 400 mmol·kg(-1)). Results demonstrate that relative water content decreased in HYPER. HYPER resulted in significant alterations in muscle metabolite concentrations (lower glycogen, elevated lactate, and glucose-6-phosphate), suggesting a decrease in energy charge. Glucose uptake was also found to be higher in HYPER, and AS160 (implicated in insulin- and contraction-mediated glucose uptake) was found to be significantly more phosphorylated in HYPER than in ISO after 30 min. In conclusion, glucose uptake and handling is altered with hyperosmotic extracellular stress in the fast-twitch EDL. The increases in glucose uptake might be facilitated through alterations in AS160 signaling after 30 to 60 min of osmotic stress.