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At least 271 records · Page 15

Localization of the ANG II type 2 receptor in the microcirculation of skeletal muscle

Only functional studies have suggested the presence of the ANG II type 2 (AT2) receptor in the microcirculation. To determine the distribution of this receptor in the rat skeletal muscle microcirculation, a polyclonal rabbit anti-rat antiserum was developed and used for immunohistochemistry and Western blot analysis. The antiserum was prepared against a highly specific and antigenic AT2-receptor synthetic peptide and was validated by competition and sensitivity assays. Western blot analysis demonstrated a prominent, single band at approximately 40 kDa in cremaster and soleus muscle. Immunohistochemical analysis revealed a wide distribution of AT2 receptors throughout the skeletal muscle microcirculation in large and small microvessels. Microanatomic studies displayed an endothelial localization of the AT2 receptor, whereas dual labeling with smooth muscle alpha-actin also showed colocalization of the AT2 receptor with vascular smooth muscle cells. Other cells associated with the microvessels also stained positive for AT2 receptors. Briefly, this study confirms previous functional data and localizes the AT2 receptor to the microcirculation. These studies demonstrate that the AT2 receptor is present on a variety of vascular cell types and that it is situated in a fashion that would allow it to directly oppose ANG II type 1 receptor actions.

NASA Discipline Cardiopulmonary↗

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

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.

Non-NASA Center↗

Reduced levels of skeletal muscle Na+K+ -ATPase in McArdle disease

We evaluated the hypothesis that impaired sarcolemmal function associated with exaggerated potassium release, impaired potassium uptake, or both may contribute to exertional fatigue and abnormal circulatory responses to exercise in McArdle disease (MD). The cellular mechanism of exertional fatigue and muscle injury in MD is unknown but likely involves impaired function of the ATPases that couple ATP hydrolysis to cellular work, including the muscle sodium potassium pump (Na+K+-ATPase). However, the concentration of muscle Na+K+ pumps in MD is not known, and no studies have related exercise increases in blood potassium concentrations to muscle Na+K+ pump levels. We measured muscle Na+K+ pumps (3H-ouabain binding) and plasma K+ in response to 20 minutes of cycle exercise in six patients with MD and in six sex-, age-, and weight-matched sedentary individuals. MD patients had lower levels of 3H-ouabain binding (231 +/- 18 pmol/g w.w., mean +/- SD, range, 210 to 251) than control subjects (317 +/- 37, range, 266 to 371, p < 0.0004), higher peak increases in plasma potassium in response to 45 +/- 7 W cycle exercise (MD, 1.00 +/- 0.15 mmol/L; control subjects, 0.48 +/- 0.09; p < 0.0001), and mean exercise heart rate responses to exercise that were 45 +/- 12 bpm greater than control subjects. Our results indicate that Na+K+ pump levels are low in MD patients compared with healthy subjects and identify a limitation of potassium reuptake that could result in sarcolemmal failure during peak rates of membrane activation and may promote exaggerated potassium-activated circulatory responses to submaximal exercise. The mechanism of the low Na+K+ pump concentrations in MD is unknown but may relate to deconditioning or to disruption of a close functional relationship between membrane ion transport and glycolysis.

Non-NASA Center↗

Intramuscular pressure varies with depth. The tibialis anterior muscle studied in 12 volunteers

Pressures in the tibialis anterior muscle were recorded at rest and during exercise with transducer-tipped catheters in 12 volunteers while they were supine or standing. The recordings were repeated with venous stasis created by an inflated tourniquet cuff on the thigh. Catheters were placed at 3 different sites in the muscle: catheter I adjacent to the deep surface of the fascia over the anterior compartment; catheter II between the fascia and the central tendon; and catheter III deep in the muscle close to the interosseous membrane. In both the supine and standing positions the intramuscular pressure at rest and the muscle relaxation pressure during exercise, obtained by catheter II, were greater than the corresponding pressures measured by the superficially located catheter I in the normal as well as in the volume loaded limb. The same conditions for pressure measurement consistently revealed lower pressures recorded by catheter III compared to II, but the difference was not significant. Our results indicate that intramuscular pressure increases centripetally, as the centrally lying tendon is approached. We conclude that pressure measurements for diagnosis of acute and chronic compartment syndromes and in ergonomic studies should be based on recordings from a standard location of the catheter within the muscle and a standard posture of the subject.

NASA Discipline Musculoskeletal↗

Changes in nerve conduction and Pi/PCr ratio during denervation-reinnervation of the gastrocsoleus muscles of rats

The purpose of this investigation was to study the changes in nerve conduction and phosphate metabolites of the gastrocsoleus muscles of rats during denervation-reinnervation. Sixteen male Sprague-Dawley rats underwent unilateral crush-denervation of the left sciatic nerves at the sciatic notch. Six rats were used for measurement of motor conduction latency and action potential amplitude of the gastrocsoleus muscle by stimulating the sciatic nerve at one, two and eight weeks after nerve crush. The other ten rats were designated for evaluation of the ratio of inorganic phosphorous (Pi) to phosphocreatine (PCr) by a 31P-phosphoenergetic spectrometer at two weeks and eight weeks after nerve crush. None of the sciatic nerves showed conduction to the gastrocsoleus at one or two weeks after nerve crush. At eight weeks postcrush, the motor conduction latency returned to within normal limits, whereas the action potential amplitude was only 55% of the normal. For the eight-week period of study, the Pi/PCr ratio of the normal control muscles ranged between 0.09 +/- 0.02 and 0.11 +/- 0.02 (mean +/- SD). The denervated muscles showed an increase of Pi/PCr ratio by 54% at two weeks postcrush, compared to the respective contralateral control sides. The ratios returned to the normal value by eight weeks postcrush. In summary, these data suggested that the metabolic recovery of the crush-denervated muscle followed the same pattern as the parameters of nerve conduction.

NASA Center JSC↗

Development of the NASA Digital Astronaut Project Muscle Model

This abstract describes development work performed on the NASA Digital Astronaut Project Muscle Model. Muscle atrophy is a known physiological response to exposure to a low gravity environment. The DAP muscle model computationally predicts the change in muscle structure and function vs. time in a reduced gravity environment. The spaceflight muscle model can then be used in biomechanical models of exercise countermeasures and spaceflight tasks to: 1) develop site specific bone loading input to the DAP bone adaptation model over the course of a mission; 2) predict astronaut performance of spaceflight tasks; 3) inform effectiveness of new exercise countermeasures concepts.

Mathematical Models↗

Temporal Changes in Astronauts’ Muscle and Cardiorespiratory Physiology Before, During and After Spaceflight

Background: NASA’s planned space exploration missions will require astronauts to safely perform extravehicular activity (EVA) and to safely egress vehicles in a variety of landing scenarios. Prolonged exposure to spaceflight can diminish tolerance for physical activity, decrease cardiovascular and sensorimotor function, and cause loss of bone mineral density, and reduced muscle mass and strength. Although exercise can mitigate these spaceflight-induced physiological decrements, little is known regarding the time-course of changes in muscle and aerobic performance during spaceflight. Furthermore, these exercise countermeasures are not fully protective. For example, maximal aerobic capacity (VO2pk), lower body muscle cross-sectional area, and strength decrease by about 10% to 15% after short- (~ 14 days) and long-duration (~ 6 months) missions on the International Space Station (ISS). Future space missions that are longer in duration and further from Earth will employ exploration vehicles that will have exercise hardware with less robust and more constrained exercise capabilities than of those available on the ISS. Thus, countermeasures will need to be optimized to protect crew health and performance on exploration-class missions that will last up to 3 years. This will require a more detailed understanding of the dynamic effects of spaceflight on human health and performance, and the ability of exercise to protect against this deconditioning, and the interaction of exercise with interrelated factors like nutrition, sleep, and environmental conditions. Methods: We will use standardized research and medical testing protocols previously validated in 1-G and 0-G to quantify the time course and the inter-individual variability of changes in physical performance, including cardiorespiratory fitness, and muscle strength, and endurance, before, during and after spaceflight missions lasting 2 months, 6 months, and 1 year. Additionally, we will use an extrapolation model to predict changes associated with 2–3-year exploration missions. Additionally, we will monitor in-flight exercise, nutrition, and sleep using in-flight assessment tools. Significance: Our testing protocols will provide valuable information for determining time course of change and the interindividual variability of spaceflight-induced deconditioning of aerobic capacity and muscle strength and endurance over the course of spaceflight missions up to and beyond 1 year. This information will be vital to assess whether humans can be physically ready for deep space exploration, such as on a mission to Mars, using current technology, or if additional mitigation strategies are necessary.

countermeasures↗

Mechanical stimulation of skeletal muscle cells mitigates glucocorticoid-induced decreases in prostaglandin production and prostaglandin synthase activity

The glucocorticoid dexamethasone (Dex) induces a decline in protein synthesis and protein content in tissue cultured, avian skeletal muscle cells, and this atrophy is attenuated by repetitive mechanical stretch. Since the prostaglandin synthesis inhibitor indomethacin mitigated this stretch attenuation of muscle atrophy, the effects of Dex and mechanical stretch on prostaglandin production and prostaglandin H synthase (PGHS) activity were examined. In static cultures, 10(-8) M Dex reduced PGF2 alpha production 55-65% and PGE2 production 84-90% after 24-72 h of incubation. Repetitive 10% stretch-relaxations of non-Dex-treated cultures increased PGF2 alpha efflux 41% at 24 h and 276% at 72 h, and increased PGE2 production 51% at 24 h and 236% at 72 h. Mechanical stimulation of Dex-treated cultures increased PGF2 alpha production 162% after 24 h, returning PGF2 alpha efflux to the level of non-Dex-treated cultures. At 72 h, stretch increased PGF2 alpha efflux 65% in Dex-treated cultures. Mechanical stimulation of Dex-treated cultures also increased PGE2 production at 24 h, but not at 72 h. Dex reduced PGHS activity in the muscle cultures by 70% after 8-24 h of incubation, and mechanical stimulation of the Dex-treated cultures increased PGHS activity by 98% after 24 h. Repetitive mechanical stimulation attenuates the catabolic effects of Dex on cultured skeletal muscle cells in part by mitigating the Dex-induced declines in PGHS activity and prostaglandin production.

NASA Discipline Musculoskeletal↗

Temporal multi-omic analysis uncovers sex-biased molecular programs underlying skeletal muscle adaptation to endurance training

Background. Exercise training is known to benefit health and reduce disease risk. While adaptations in skeletal muscles are fundamental to many of the health benefits of exercise training, the common and sex-specific molecular regulators that mediate these adaptations remain to be fully elucidated. Methods. To this end, we leveraged skeletal muscle multi-omics data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), where 6 month-old male and female rats endurance trained for 1, 2, 4, or 8 weeks. Our objective was to identify shared and sex-specific multi-omic molecular responses to endurance training in skeletal muscle, and relate them to phenotypic adaptations. Results. We identified largely sexually-conserved transcriptomic and proteomic enrichments in the gastrocnemius, which correlated with skeletal muscle responses from a published exercise study in humans. We uncovered sex-consistent post-translational modifications, including decreased oxidation of MYH2 and deacetylation of the ß-oxidation enzyme HADHA. Pathway enrichment analyses revealed sex-specific remodeling across the acetylome, redox proteome, and phosphoproteome; females decreased mitochondrial protein oxidation and increased mitochondrial cristae proteins, indicative of enhanced redox buffering and mitochondrial efficiency. Despite observed decreases in the oxidation of key mitochondrial proteins, females displayed increases in the oxidation of proteins involved in glucose catabolism relative to males after 8 weeks of training, suggestive of sex-biased subcellular reactive oxygen species generation. Conclusions. This work shows a large portion of the adaptive response to endurance training in skeletal muscle is shared between females and males, while there are distinct and nuanced sex-specific adaptations that are evident, particularly at the level of post-translational regulation.

Many, Gina M.↗

Subminiature transducers for measuring forces and deformation of heart muscle

Two subminiature transducers, one measuring muscle forces and one measuring muscle displacement, can be inserted into heart muscle without interfering with it. Probe, approximately 1 mm (0.04 in), causes no damage to heart muscle. Probe can be rotated to different positions to measure muscle forces from various directions.

Feldstein, C.↗

Evaluation of localized muscle fatigue using power spectral density analysis of the electromyogram

Surface electromyograms (EMGs) taken from three upper torso muscles during a push-pull task were analyzed by a power spectral density technique to determine the operational feasibility of the technique for identifying changes in the EMGs resulting from muscular fatigue. The EMGs were taken from four subjects under two conditions (1) in shirtsleeves and (2) in a pressurized space suit. This study confirmed that frequency analysis of dynamic muscle activity is capable of providing reliable data for many industrial applications where fatigue may be of practical interest. The results showed significant effects of the pressurized space suit on the pattern of shirtsleeve fatigue responses of the muscles. The data also revealed (1) reliable differences between muscles in fatigue-induced responses to various locations in the reach envelope at which the subjects were required to perform the push-pull exercise and (2) the differential sensitivity of muscles to the various reach positions in terms of fatigue-related shifts in EMG power.

Lafevers, E. V.↗

Biochemical adaptations of antigravity muscle fibers to disuse atrophy

Studies are presented in four parts of this report. The four parts include; (1) studies to gain information on the molecular basis of atrophy by antigravity muscle; (2) studies on the work capacity of antigravity muscles during atrophy and during recovery from atrophy; (3) studies on recovery of degenerated antigravity fibers after removal of hind-limb casts; and (4) studies on the atrophy and recovery of bone. The philosophy of these studies was to identify the time sequence of events in the soleus muscle of the rat following immobilization of the hind limbs, so that the length of the soleus muscle within the fixed limb is less than its resting length. In two separate studies, no decline in the weight of the soleus muscle could be detected during the first 72 hours of limb immobilization.

Booth, F. W.↗

Development of a bedrest muscle stress apparatus

In attempting further to define the deleterious effects of spaceflight on the human body, measurement systems and techniques were devised to determine the loss of skeletal muscle strength and tone as a result of spaceflight exposure. In order to determine how the muscle degradation process progresses with time during nonuse, a system for measuring muscle stress during bedrest was developed. The Bedrest Muscle Stress Apparatus is configured to slip snugly over the foot board of a standard hospital bed. Data collected with this device correlated well with pre- and post-bedrest data collected with the original skeletal muscle stress apparatus.

Booher, C. R.↗

Operator performance and localized muscle fatigue in a simulated space vehicle control task

Fourier transforms in a special purpose computer were utilized to obtain power spectral density functions from electromyograms of the biceps brachii, triceps brachii, brachioradialis, flexor carpi ulnaris, brachialis, and pronator teres in eight subjects performing isometric tracking tasks in two directions utilizing a prototype spacecraft rotational hand controller. Analysis of these spectra in general purpose computers aided in defining muscles involved in performing the task, and yielded a derived measure potentially useful in predicting task termination. The triceps was the only muscle to show significant differences in all possible tests for simple effects in both tasks and, overall, was the most consistently involved of the six muscles. The total power monitored for triceps, biceps, and brachialis dropped to minimal levels across all subjects earlier than for other muscles. However, smaller variances existed for the biceps, brachioradialis, brachialis, and flexor carpi ulnaris muscles and could provide longer predictive times due to smaller standard deviations for a greater population range.

Lewis, J. L., Jr.↗

Fluid shifts and muscle function in humans during acute simulated weightlessness

The acute effects of simulated weightlessness on transcapillary fluid balance, tissue fluid shifts, muscle function, and triceps surface reflex time were studied in eight supine human subjects who were placed in a 5 degrees head-down tilt position for 8 hr. Results show a cephalic fluid shift from the legs as indicated by facial edema, nasal congestion, increased urine flow, decreased creatinine excretion, reduced calf girth, and decreased lower leg volume. The interstitial fluid pressure in the tibialis anterior muscle and subcutaneous tissue of the lower leg was found to fall significantly, while other transcapillary pressures (capillary and interstitial fluid colloid osmotic pressures) were relatively unchanged. The total water content of the soleus muscle was unchanged during the head-down tilt. After head-down tilt, isometric strength and isokinetic strength of the plantar flexors were unchanged, while the triceps surae reflex time associated with plantar flexion movement slowed slightly. These results demonstrate a dehydration effect of head-down tilt on muscle and subcutaneous tissue of the lower leg that may affect muscle function.

Hargens, A. R.↗

Rat hindlimb muscle responses to suspension hypokinesia/hypodynamia

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.

Musacchia, X. J.↗

Glucose uptake and glycogen synthesis in muscles from immobilized limbs

Defects in glucose metabolism in muscles of immobilized limbs of mice were related to alterations in insulin binding, insulin responsiveness, glucose supply, and insulin activation of glycogen synthase. These were tested by in vitro methodology. A significant lessening in the insulin-induced maximal response of 2-deoxyglucose uptake into the mouse soleus muscle occurred between the 3rd and 8th h of limb immobilization, suggesting a decreased insulin responsiveness. Lack of change in the specific binding of insulin to muscles of 24-h immobilized limbs indicates that a change in insulin receptor number did not play a role in the failure of insulin to stimulate glucose metabolism. Its inability to stimulate glycogen synthesis in muscle from immobilized limbs is due, in part, to a lack of glucose supply to glycogen synthesis and also to the ineffectiveness of insulin to increase the percentage of glycogen synthase in its active form in muscles from 24-h immobilized limbs.

Nicholson, W. F.↗

No effect of sex steroids on compensatory muscle hypertrophy

The effects of orchiectomy and/or subcutaneously implanted testosterone propionate (TP) on the hypertrophic response of rat plantaris muscles to functional overload (induced by bilateral removal of gastrocnemius and soleus muscles) are investigated experimentally. Muscle wet weight, metabolic substrate oxidation, and cytosolic androgen-receptor binding are measured, and the results are presented in tables. Eight weeks after surgery, the plantaris muscle weight as a percentage of body weight is found to be about twice that in rats without muscle overload, regardless of the sex-hormone status. Overloading causes decreased ability to oxidize glucose and pyruvate, decreased succinate dehydrogenase specific activity, and no change in the ability to oxidize beta-hydroxybutyrate or in androgen-receptor binding. The oxidative response is unaffected by orchiectomy or TP or both. It is argued that the actions of sex hormones and functional overload are not synergistic.

Max, S. R.↗