Physiological and pharmacological studies on nematodes

Classical transmitters and neuroactive peptides act as transmitters or modulators within the central and peripheral nervous systems of nematodes, for example Ascaris suum and Caenorhabditis elegans. Acetylcholine (ACh) and gamma-aminobutyric acid (GABA) are respectively the excitatory and inhibitory transmitters onto somatic body wall muscle while 5-hydroxytrypamine (5-HT) is the excitatory transmitter onto pharyngeal muscle. 5-HT also reduces ACh-induced contractions of somatic muscle and this action of 5-HT is mediated through activation of adenylate cyclase while that on pharyngeal muscle is mediated through inositol phosphate activation. Glutamate, dopamine and octopamine also have transmitter roles in nematodes. Neuroactive peptides of the RFamide family can excite somatic muscle, for example, AF-1 (KNEFIRFamide), AF-2 (KHEYLRFamide), AF-3 (AVPGVLRFamide) and AF-4 (GDVPGVLRFamide) or inhibit and relax this muscle, for example, PF-1 (SDPNFLRFamide), PF-2 (SADPNFLRFamide) and PF-4 (KPNlRFamide). In addition PF-3 (AF-8) (KSAYMRFamide) has a biphasic action on pharyngeal muscle, excitation followed by inhibition while AF-1 only inhibits this muscle. The peptide effects can be either pre- or postsynaptic or both and are likely to be mediated through second messenger systems. In addition these peptides modulate the action of classical transmitters, particularly ACh.     

Effect of anabolic steroids on overloaded and overloaded suspended skeletal muscle

The purpose of this study was to ascertain whether anabolic steroids act synergistically with functional overload in terms of increasing muscle weight and subcellular protein content of normal overloaded and suspended overloaded rodent plantaris muscle. Female rats were randomly assigned to six groups (7 rats/group) for 6 wk: 1) normal control (NC), 2) overload (OV), 3) overload steroid (OV-S), 4) normal suspended (N-SUS), 5) overload suspended (OV-SUS), and 6) overload suspended steroid (OV-SUS-S). Rats receiving anabolic steroid were administered 0.3 mg nandrolone decanoate (Deca-Durabolin) per day. Relative to control values, overload induced 1) sparing of muscle weight of the OV-SUS group as well as larger absolute and normalized (mg muscle/g body wt) muscle weight of the OV group (P less than 0.05), 2) greater protein content (mg/muscle, P less than 0.05), and 3) an increased relative expression of slow myosin in both the OV and OV-SUS groups (P less than 0.05). Although anabolic steroid treatment of overload animals (OV-S) did not alter further the pattern of response of any parameter analyzed for the OV group, it did induce larger absolute and normalized muscle weight (P less than 0.05) as well as a greater protein content (mg/muscle, P less than 0.05) of the OV-SUS-S group compared with control values. However, anabolic steroid treatment did not alter the pattern of isomyosin expression observed in the overload (OV-S vs. OV) or overload suspended (OV-SUS-S vs. OV-SUS) groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuropeptide Y: presence in perivascular noradrenergic neurons and vasoconstrictor effects on skeletal muscle blood vessels in experimental animals and man

The presence of neuropeptide Y (NPY)-like immunoreactivity (-LI) in sympathetic perivascular nerves and the functional effects of NPY and noradrenaline (NA) on vascular tone were studied in skeletal muscle of various species. A dense network of NPY-LI was found around arteries and arterioles but not venules in the gluteus maximus muscle of man, gracilis muscle of dog, tenuissimus muscle of rabbit and quadriceps muscle of cat, rat, guinea pig and pig. The distribution of NPY-immunoreactive (-IR) nerves was closely correlated to the presence of tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH)-positive fibers, two markers for noradrenergic neurons. Double-staining experiments revealed that NPY- and TH-IR as well as NPY- and DBH-IR nerve fibers around arteries and arterioles were identical. The veins and venules, however, lacked or had a very sparse innervation of NPY-, TH- and DBH-positive fibers. The NPY- and TH-IR nerves in quadriceps muscle of the guinea pig were absent after treatment with 6-hydroxydopamine. Lumbosacral sympathetic ganglia from the same species contained many NPY-positive cells which were also TH- and DBH-IR. NPY-LI was also detected by radioimmunoassay in extracts of skeletal muscle from guinea pig, rabbit, dog, pig and man as well as of lumbosacral sympathetic ganglia. The content of NPY-LI in skeletal muscle was relatively low (0.1-0.4 pmol/g), whereas lumbosacral sympathetic ganglia had a much higher content (48-88 pmol/g). NPY (10(-7) M) contracted arterioles in the tenuissimus muscle of the rabbit to a similar extent (by 65%) as NA (10(-6) M), as studied by intravital microscopy in vivo. NPY had no effect on the corresponding venules while NA caused a slight contraction of these vessels. In vitro studies of small human skeletal muscle arteries and veins revealed that NPY was more potent than NA in contracting the arteries, and the highest concentration of NPY (5 x 10(-7) M) caused a contraction of a similar magnitude as NA 10(-5) M. NA contracted veins from human skeletal muscle, while NPY had only small effects. It is suggested that NPY, together with NA, could be of importance for sympathetic control of skeletal muscle blood flow.     

Effects of inter- and extramuscular myofascial force transmission on adjacent synergistic muscles: assessment by experiments and finite-element modeling

The effects of inter- and extramuscular myofascial force transmission on muscle length force characteristics were studied in rat. Connective tissues at the bellies of the experimental synergistic muscles of the anterior crural compartment were left intact. Extensor digitorium longus (EDL) muscle was lengthened distally whereas tibialis anterior (TA) and extensor hallucis longus (EHL) were kept at constant muscle–tendon complex length. Substantial differences were found in EDL force measured at the proximal and distal tendons (maximally 46% of the proximal force). EDL with intact inter- as well as extramuscular connections had an increased length range between active slack and optimum length compared to EDL with extramuscular connections exclusively: optimum muscle length was shifted by more than 2 mm. Distal EDL lengthening caused the distal force exerted by TA+EHL complex to decrease (approximately 17% of the initial force). This indicates increased intermuscular myofascial force transmission from TA+EHL muscle complex to EDL muscle.

Finite-element modeling showed that: (1) Inter- and extramuscular myofascial force transmission leads to a substantial distribution of the lengths of the sarcomeres arranged in series within muscle fibers. Distribution of stress within the muscle fibers showed that the muscle fiber cannot be considered as a unit exerting equal forces at both ends. (2) Increased heterogeneity of mean fiber sarcomere lengths (i.e., a “parallel” distribution of length of sarcomeres among different muscle fibers) is found, particularly at high muscle lengths. This also explains the shift in muscle optimum length to higher lengths.

It is concluded that inter- and extramuscular myofascial force transmission has substantial effects on muscle length–force characteristics.     

Intracellular signals involved in the effects of insulin-like growth factors and neuregulins on myofibre formation

A number of extracellular factors are involved in the embryonic development of skeletal muscle and the muscle regeneration that is triggered in response to muscle damage. Some of them, such as insulin-like growth factors (IGFs), fibroblast growth factors (FGFs), hepatocyte growth factor (HGF), transforming growth factor (TGF)-like molecules, leukemia inhibitor factor (LIF) or platelet-derived growth factors (PDGFs), are involved in the activation of cell proliferation that operates before muscle differentiation. In addition, factors such as IGFs, neuregulins (NRGs), sonic hedgehog (Shh) or Wnt promote muscle differentiation. Here, we review the intracellular signals that are triggered in the myogenic effect of IGFs and neuregulin and we describe common pathways. A fuller understanding of the signalling pathways triggered by these factors may permit the design of new tools for muscle regeneration therapy.     

Anabolic actions of a mixed beta-adrenergic agonist on nitrogen retention and protein turnover.

Subcutaneous administration of a mixed beta-agonist induced increases in muscle (+13%) and heart (+17%) weights, which were accompanied by a reduction in back (-13%) and perirenal (-27%) fat stores in young male rats, while no changes in liver were observed. The values of nitrogen retention (mg/day) were significantly higher in the beta-agonist treated animals (+16%) as well as those of muscle DNA content (+8%). On the other hand, no statistically significant changes in muscle protein synthetic activity (g protein synthetized/g RNA) were detected (control: 13.4 vs treated: 14.6), while muscle proteolytic activity was decreased (-9%) in those rats administered with the repartitioning agent. In this context, it is suggested that the anabolic effect of metaproterenol should be attributed to a reduction in muscle protein degradation rather than to changes in protein synthesis.     

Mechanism of insulin's anabolic effect on muscle: measurements of muscle protein synthesis and breakdown using aminoacyl-tRNA and other surrogate measures

Despite being an anabolic hormone in skeletal muscle, insulin's anticatabolic mechanism in humans remains controversial, with contradictory reports showing either stimulation of protein synthesis (PS) or inhibition of protein breakdown (PB) by insulin. Earlier measurements of muscle PS and PB in humans have relied on different surrogate measures of aminoacyl-tRNA and intracellular pools. We report that insulin's effect on muscle protein turnover using aminoacyl-tRNA as the precursor of PS and PB is calculated by mass balance of tracee amino acid (AA). We compared the results calculated from various surrogate measures. To determine the physiological role of insulin on muscle protein metabolism, we infused tracers of leucine and phenylalanine into 18 healthy subjects, and after 3 h, 10 subjects received a 4-h femoral arterial infusion of insulin (0.125 mUxkg(-1)xmin(-1)), while eight subjects continued with saline. Tracer-to-tracee ratios of leucine, phenylalanine, and ketoisocaproate were measured in the arterial and venous plasma, muscle tissue fluid, and AA-tRNA to calculate muscle PB and PS. Insulin infusion, unlike saline, significantly reduced the efflux of leucine and phenylalanine from muscle bed, based on various surrogate measures which agreed with those based on leucyl-tRNA (-28%), indicating a reduction in muscle PB (P < 0.02) without any significant effect on muscle PS. In conclusion, using AA-tRNA as the precursor pool, it is demonstrated that, in healthy humans in the postabsorptive state, insulin does not stimulate muscle protein synthesis and confirmed that insulin achieves muscle protein anabolism by inhibition of muscle protein breakdown.     

Effects of long-term starvation on body weight and body composition of juvenile channel catfish, Ictalurus punctatus, with special emphasis on amino acid and fatty acid changes

Triplicate groups of 30 channel catfish Ictalurus punctatus (initial weight: 76.13 ± 0.78 g) were stocked in indoor flow‐through fiberglass tanks and starved for 80 days. Body weight, morphometric parameters, body composition, amino acid and fatty acid changes in muscle and liver tissues were investigated to determine the effect of long‐term starvation on body weight and body composition of juvenile channel catfish. During the starvation period, body weight, condition factor (CF), viscerosomatic index (VSI), hepatosomatic index (HSI) and intraperitoneal fat ratio (IPR) declined (P < 0.05). In the whole body, both protein and lipid decreased while changes in the amount of fat were relatively rapid. Hepatic lipid and carbohydrate contents declined as starvation progressed, but crude protein and moisture contents increased (P < 0.05). In contrast, muscle crude protein showed a greater decline than did muscle lipids, and muscle glycogen remained relatively constant. During the 80‐day starvation period the ratio of total essential amino acids (EAA) to total non‐essential amino acids (NEAA) in muscle and liver (P < 0.05) increased. In muscle tissue, total mono‐unsaturated fatty acids (MUFA) and n‐6 fatty acids decreased, but total saturated fatty acids (SFA) and n‐3 fatty acids, as well as the ratio of n‐3 to n‐6 fatty acids increased (P < 0.05). However, in the liver, starvation resulted in the relative increase of total MUFA and reduction in n‐3 fatty acid contents as well as the ratio of n‐3 to n‐6 fatty acids (P < 0.05). Based on these observations, lipids and glycogen can be considered as more important sources of catabolizable energy in liver, whereas protein might be preferentially mobilized in muscle; lipids played a more important role as energy reserves on a relative basis in the whole body. Channel catfish preferentially utilized NEAA to EAA as an energy substrate and preferentially reserved EAA during starvation. Mobilization of fatty acids showed more variation in the muscle and liver during starvation.     

Substantial effects of epimuscular myofascial force transmission on muscular mechanics have major implications on spastic muscle and remedial surgery

The specific aim of this paper is to review the effects of epimuscular myofascial force transmission on muscular mechanics and present some new results on finite element modeling of non-isolated aponeurotomized muscle in order to discuss the dependency of mechanics of spastic muscle, as well as surgery for restoration of function on such force transmission.

The etiology of the effects of spasticity on muscular mechanics is not fully understood. Clinically, such effects feature typically a limited joint range of motion, which at the muscle level must originate from altered muscle length–force characteristics, in particular a limited muscle length range of force exertion. In studies performed to understand what is different in spastic muscle and what the effects of remedial surgery are, muscle is considered as being independent of its surroundings. Conceivably, this is because the classical approach in muscle mechanics is built on experimenting with dissected muscles. Certainly, such approach allowed improving our understanding of fundamental muscle physiology yet it yielded implicitly a narrow point of view of considering muscle length–force characteristics as a fixed property of the muscle itself.

However, within its context of its intact connective tissue surroundings (the in vivo condition) muscle is not an isolated and independent entity. Instead, collagenous linkages between epimysia of adjacent muscles provide direct intermuscular connections, and structures such as the neurovascular tracts provide indirect intermuscular connections. Moreover, compartmental boundaries (e.g., intermuscular septa, interosseal membranes, periost and compartmental fascia) are continuous with neurovascular tracts and connect muscular and non-muscular tissues at several locations additional to the tendon origins and insertions. Epimuscular myofascial force transmission occurring via this integral system of connections has major effects on muscular mechanics including substantial proximo-distal force differences, sizable changes in the determinants of muscle length–force characteristics (e.g. a condition dependent shift in muscle optimum length to a different length or variable muscle optimal force) explained by major serial and parallel distributions of sarcomere lengths. Therefore, due to epimuscular myofascial force transmission, muscle length–force characteristics are variable and muscle length range of force exertion cannot be considered as a fixed property of the muscle.

The findings reviewed presently show that acutely, the mechanical mechanisms manipulated in remedial surgery are dominated by epimuscular myofascial force transmission. Conceivably, this is also true for the mechanism of adaptation during and after recovery from surgery. Moreover, stiffened epimuscular connections and therefore a stiffened integral system of intra- and epimuscular myofascial force transmission are indicated to affect the properties of spastic muscle. We suggest that important advancements in our present understanding of such properties, variability in the outcome of surgery and considerable recurrence of the impeded function after recovery cannot be made without taking into account the effects of epimuscular myofascial force transmission.     

骨骼肌卫星细胞对肉品质的影响及其分化调控

骨骼肌卫星细胞是一种肌源性干细胞, 在骨骼肌的生长、发育及肌肉损伤修复中有着至关重要的作用。肌卫星细胞通过增殖、分化融合肌纤维形成新的肌核从而导致骨骼肌纤维的肥大以及骨骼肌纤维类型的相互转化, 进而影响肉品质的形成。文章从肌纤维的发育与肉品质形成、卫星细胞分化与肌纤维特征的相关性等方面, 对卫星细胞的Notch等经典遗传信号通路和miRNA等表观遗传调控及其对肉品质的影响进行了综述。     

Relationship between muscle length and moment arm on EMG activity of human triceps surae muscle.

PURPOSE: The purpose of this experiment was to evaluate the effects of both muscle length and moment arm (MA) on the electromyographic (EMG) and force output of the triceps surae (TS) muscle. RELEVANCE: It is well recognized that changes in muscle length affect both the muscle's force generating capacity as well as its twitch speed. This relationship is well established in animal preparations. Contrary to animal experiments where length can be directly manipulated in isolated muscles, human experiments require that all muscle length changes be secondary to changes in a joint angle. Such experimental manipulations therefore produce changes in not only muscle length, but also in the muscle's MA. The relative effect of muscle length and MA changes on muscle EMG has not been determined in previous experiments. METHODS: This study was executed in two phases. First, using fresh human cadaver lower limbs, data were gathered describing the relationship between knee and ankle angle changes for maintenance of a constant TS muscle length, while its MA at the ankle joint has been changed. In the second phase of the study, results obtained from phase one were applied to 10 healthy adult human subjects to measure the EMG (surface and fine wire) activity of TS at three different conditions: when both length and MA were shortened, when muscle length was decreased given a constant MA and when MA was shortened given a constant muscle length. RESULTS: A significant increase in muscle activity was found as both the length and MA of TS muscle were shortened. A similar pattern of increased muscle activity was observed when the MA was shortened given a constant muscle length. No significant change in TS activity was found when muscle length was shortened, given a constant MA at the ankle joint. CONCLUSIONS: The findings of this study indicate that changes in the Achilles tendon MA predominate over the muscle length variations in determining the level of TS activity when generating plantar flexion torque.     

Adrenergic and serotonergic regulation of skeletal muscle metabolism in rat. I. The effects of adrenergic and serotonergic antagonists on the regulation of muscle amino acid release, glycogenolysis, and cyclic nucleotide levels

The biochemical mechanisms of serotonergic and adrenergic action on skeletal muscle cyclic nucleotide, glycogen, and amino acid metabolism have been investigated in intact rat epitrochlaris skeletal muscle preparations. Endogenous catecholamine levels in these preparations were 28.6 +/- 2.1 pg/mg of muscle. Release of these catecholamines by tyramine produced a 25% inhibition of alanine and glutamine release. Pretreatment of animals in vivo with 6-hydroxydopamine depleted catecholamine content by 85%. On incubation, preparations from these pretreated animals showed no effect of tyramine on amino acid metabolism. Serotonin (10(-5) M) and epinephrine (10(-5) M) inhibited alanine and glutamine release equally in preparations from 6-hydroxydopamine-pretreated as compared to control rats. Adrenergic antagonists such as dl-propranolol (10(-8)-10(-6) M), oxprenolol (10(-8)-10(-6) M), and practolol (10(-6)-10(-4) M) blocked equally the inhibition of alanine and glutamine release, prevented the stimulations of muscle cAMP levels, phosphosphorylase a formation, and the depletion of muscle glycogen produced by either epinephrine or serotonin. In contrast, serotonergic antagonists such as methysergide (10(-8)-10(-6) M) and cyproheptadine (10(-8)-10(-6) M) blocked the inhibition of alanine and glutamine release, the stimulations of muscle cAMP levels and phosphorylase a formation, and the decreased muscle glycogen content effected by serotonin but not by epinephrine. Incubation of muscles with both epinephrine and serotonin together produced additive stimulation of muscle cAMP levels, but not of the inhibition of alanine and glutamine release. These data indicate that the action of these agonists on skeletal muscle protein and amino acid, glycogen, and cyclic nucleotide metabolism proceeds directly via separate and discrete serotonergic and adrenergic receptor-adenylyl cyclase mechanisms in skeletal muscle.     

Effects of exercise in normoxia and acute hypoxia on respiratory muscle metabolites

We determined changes in rat plantaris, diaphragm, and intercostal muscle metabolites following exercise of various intensities and durations, in normoxia and hypoxia (FIO2 = 0.12). Marked alveolar hyperventilation occurred during all exercise conditions, suggesting that respiratory muscle motor activity was high. [ATP] was maintained at rest levels in all muscles during all normoxic and hypoxic exercise bouts, but at the expense of creatine phosphate (CP) in plantaris muscle and diaphragm muscle following brief exercise at maximum O2 uptake (VO2max) in normoxia. In normoxic exercise plantaris [glycogen] fell as exercise exceeded 60% VO2max, and was reduced to less than 50% control during exhaustive endurance exercise (68% VO2max for 54 min and 84% for 38 min). Respiratory muscle [glycogen] was unchanged at VO2max as well as during either type of endurance exercise. Glucose 6-phosphate (G6P) rose consistently during heavy exercise in diaphragm but not in plantaris. With all types of exercise greater than 84% VO2max, lactate concentration ([LA]) in all three muscles rose to the same extent as arterial [LA], except at VO2max, where respiratory muscle [LA] rose to less than half that in arterial blood or plantaris. Exhaustive exercise in hypoxia caused marked hyperventilation and reduced arterial O2 content; glycogen fell in plantaris (20% of control) and in diaphragm (58%) and intercostals (44%). We conclude that respiratory muscle glycogen stores are spared during exhaustive exercise in the face of substantial glycogen utilization in plantaris, even under conditions of extreme hyperventilation and reduced O2 transport. This sparing effect is due primarily to G6P inhibition of glycogen phosphorylase in diaphragm muscle. The presence of elevated [LA] in the absence of glycogen utilization suggests that increased lactate uptake, rather than lactate production, occurred in the respiratory muscles during exhaustive exercise.     

Effects of Blood Flow Restricted Low-Intensity Concentric or Eccentric Training on Muscle Size and Strength

We investigated the acute and chronic effects of low-intensity concentric or eccentric resistance training with blood flow restriction (BFR) on muscle size and strength. Ten young men performed 30% of concentric one repetition maximal dumbbell curl exercise (four sets, total 75 reps) 3 days/week for 6 weeks. One arm was randomly chosen for concentric BFR (CON-BFR) exercise only and the other arm performed eccentric BFR (ECC-BFR) exercise only at the same exercise load. During the exercise session, iEMG for biceps brachii muscles increased progressively during CON-BFR, which was greater (p<0.05) than that of the ECC-BFR. Immediately after the exercise, muscle thickness (MTH) of the elbow flexors acutely increased (p<0.01) with both CON-BFR and ECC-BFR, but was greater with CON-BFR (11.7%) (p<0.01) than ECC-BFR (3.9%) at 10-cm above the elbow joint. Following 6-weeks of training, MRI-measured muscle cross-sectional area (CSA) at 10-cm position and mid-upper arm (12.0% and 10.6%, respectively) as well as muscle volume (12.5%) of the elbow flexors were increased (p<0.01) with CON-BFR. Increases in muscle CSA and volume were lower in ECC-BFR (5.1%, 0.8% and 2.9%, respectively) than in the CON-BFR and only muscle CSA at 10-cm position increased significantly (p<0.05) after the training. Maximal voluntary isometric strength of elbow flexors was increased (p<0.05) in CON-BFR (8.6%), but not in ECC (3.8%). These results suggest that CON-BFR training leads to pronounced acute changes in muscle size, an index of muscle cell swelling, the response to which may be an important factor for promoting muscle hypertrophy with BFR resistance training.     

Influence of locomotion speed on biomechanical subtask and muscle synergy

This paper investigates the relationship of biomechanical subtasks, and muscle synergies with various locomotion speeds. Ground reaction force (GRF) of eight healthy subjects is measured synchronously by force plates of treadmill at five different speeds ranging from 0.5 m/s to 1.5 m/s. Four basic biomechanical subtasks, body support, propulsion, swing, and heel strike preparation, are identified according to GRF. Meanwhile, electromyography (EMG) data, used to extract muscle synergies, are collected from lower limb muscles. EMG signals are segmented periodically based on GRF with the heel strike as the split points. Variability accounted for (VAF) is applied to determine the number of muscle synergies. We find that four muscle synergies can be extracted in all five situations by non-negative matrix factorization (NMF). Furthermore, the four muscle synergies and biomechanical subtasks keep invariant as the walking speed changes.     

Effects of prolonged undernutrition on structure and function of the diaphragm

The present study examined the effect of prolonged undernutrition on diaphragmatic structure and force-generating ability. Studies were performed on 58 Syrian hamsters in which the feed was reduced by 33% for a 4-wk period. Sixty animals fed a similar diet ad libitum served as controls. Diaphragm muscle structure was assessed from its mass (wet and dry weight), thickness, fiber composition, and fiber size. Isometric force produced in vitro by isolated muscle strips in response to electrical stimulation of the phrenic nerve was examined over a range of muscle lengths (length-tension relationship). In undernourished animals, body weight decreased 25 +/- 5%. Diaphragm wet and dry weight, muscle thickness, and the cross-sectional area of fast-glycolytic (FG) and fast-oxidative (FO) fibers were significantly less in undernourished than control animals and correlated with reductions in body weight. The cross-sectional area of slow-oxidative (SO) fibers was the same in the two groups. The percentage of FG fibers in undernourished animals was decreased slightly and the percentage of SO fibers increased. Maximum isometric tension was reduced in undernourished animals as compared with controls, but the position and shape of the length-tension relationship was the same in the two groups. Reductions in muscle force appeared to be explained by decreases in muscle mass, since tension corrected for cross-sectional area or tissue weight was the same in the two groups. Therefore muscle mechanical efficiency appeared to be unaffected by undernutrition. These data indicate that prolonged undernutrition causes deleterious changes in diaphragm muscle structure that impair its ability to generate force.     

Effect of insulin on human skeletal muscle protein synthesis is modulated by insulin-induced changes in muscle blood flow and amino acid availability

Insulin promotes muscle anabolism, but it is still unclear whether it stimulates muscle protein synthesis in humans. We hypothesized that insulin can increase muscle protein synthesis only if it increases muscle amino acid availability. We measured muscle protein and amino acid metabolism using stable-isotope methodologies in 19 young healthy subjects at baseline and during insulin infusion in one leg at low (LD, 0.05), intermediate (ID, 0.15), or high (HD, 0.30 mUxmin(-1)x100 ml(-1)) doses. Insulin was infused locally to induce muscle hyperinsulinemia within the physiological range while minimizing the systemic effects. Protein and amino acid kinetics across the leg were assessed using stable isotopes and muscle biopsies. The LD did not affect phenylalanine delivery to the muscle (-9 +/- 18% change over baseline), muscle protein synthesis (16 +/- 26%), breakdown, or net balance. The ID increased (P < 0.05) phenylalanine delivery (+63 +/- 38%), muscle protein synthesis (+157 +/- 54%), and net protein balance, with no change in breakdown. The HD did not change phenylalanine delivery (+12 +/- 11%) or muscle protein synthesis (+9 +/- 19%), and reduced muscle protein breakdown (-17 +/- 15%), thus improving net muscle protein balance but to a lesser degree than the ID. Changes in muscle protein synthesis were strongly associated with changes in muscle blood flow and phenylalanine delivery and availability. In conclusion, physiological hyperinsulinemia promotes muscle protein synthesis as long as it concomitantly increases muscle blood flow, amino acid delivery and availability.     

Influence of sex and active muscle mass on renal vascular responses during static exercise

During exercise, reflex renal vasoconstriction helps maintain blood pressure and redistributes blood flow to the contracting muscle. Sex and muscle mass have been shown to influence certain cardiovascular responses to exercise. Whether sex and/or muscle mass influence renal vasoconstrictor responses to exercise is unknown. We studied healthy men (n = 10) and women (n = 10) matched for age and body mass index during handgrip (HG, small muscle mass) and quadriceps contraction (QC, large muscle mass) as beat-to-beat changes in renal blood flow velocity (RBV; duplex ultrasound), mean arterial pressure (MAP; Finapres), and heart rate (ECG) were monitored. Renal vascular resistance (RVR) index was calculated as MAP / RBV. Responses to HG vs. QC were compared in 13 subjects. We found that 1) RVR responses to short (15-s) bouts and fatiguing HG were similar in men and women (change in RVR during 15-s HG at 70% of maximum voluntary contraction = 23 +/- 4 and 31 +/- 4% in men and women, respectively, P = not significant); 2) post-HG circulatory responses were similar in men and women; and 3) HG and QC were similar during short (15-s) bouts (change in RVR during HG at 50% of maximum voluntary contraction = 19 +/- 3 and 18 +/- 5% for arm and leg, respectively, P = not significant). Our findings suggest that muscle reflex-mediated renal vasoconstriction is similar in men and women during static exercise. Moreover, muscle mass does not contribute to the magnitude of the reflex renal vasoconstrictor response seen with muscle contraction.     

The effects of dynamic tension and reduced graft size on muscle regeneration in rabbit free muscle grafts.

In a study of 28 adult New Zealand White rabbits, the influence of tension and size on muscle regeneration in tibialis anterior free muscle grafts (without vascular anastomoses) was examined 6 months after transplantation. Three laboratory models were studied: (1) whole dynamic (WD) graft (allowing ankle excursion and, therefore, variable dynamic physiologic tension), (2) whole static (WS) graft (constant, fixed length and, thus, only isometric tension), and (3) longitudinally sliced (reduced radius) dynamic (SD) model. Bilateral orthotopic grafts of the tibialis anterior muscle were performed in 24 rabbits (eight animals in each of the three different model groups). Controls consisted of normal tibialis anterior muscle from four age-matched rabbits. All tibialis anterior muscle grafts were examined histologically (fiber counts) and functionally (determined by in situ contractile properties under maximal stimulation conditions). The WD grafts demonstrated a significantly higher number of regenerated fibers per muscle cross section (4819 +/- 589) than the WS (2221 +/- 603) or SD (1919 +/- 732) grafts. The amount of tetanic tension in the WD grafts was 35 percent of the control and twice as much as that of the WS grafts (WD 1.0 +/- 0.2 kg versus WS 0.5 +/- 0.4 kg; p less than 0.05). The SD grafts produced approximately one-third as much maximum tetanic tension as the WD grafts (0.3 +/- 0.1 kg versus 1.0 +/- 0.2 kg), demonstrating that the amount of recovery was similar in these two dynamic models, since only the longitudinal middle third of the muscle was grafted in the SD model. Free muscle grafts under dynamic tension, which allows excursion, have shown a greater amount of muscle-fiber regeneration and restoration of function compared with a graft with fixed length. The positive effect of dynamic mechanical tension on small autogenous free muscle grafts (without vascular anastomoses) is clinically significant in the reconstruction of facial and hand neuromuscular deficits when blood vessels are not available for reanastomosis. Future studies using the tibialis anterior WD and SD transplant models will strengthen our understanding of the events of spontaneous revascularization and skeletal muscle regeneration.