Time course of human skeletal muscle nitrate and nitrite concentration changes following dietary nitrate ingestion

Nitrate ([Formula: see text]) ingestion has been shown to have vasoactive and ergogenic effects that have been attributed to increased nitric oxide (NO) production. Recent observations in rodents suggest that skeletal muscle tissue serves as an endogenous [Formula: see text] “reservoir.” The present study determined [Formula: see text] contents in human skeletal muscle tissue in a postabsorptive state and following ingestion of a sodium nitrate bolus (NaNO3). Seventeen male, type 2 diabetes patients (age 72 ± 1 yr; body mass index 26.5 ± 0.5 kg/m2; means ± SE) were randomized to ingest a dose of NaNO3 (NIT; 9.3 mg [Formula: see text]/kg body wt) or placebo (PLA; 8.8 mg NaCl/kg body wt). Blood and muscle biopsy samples were taken before and up to 7 h following [Formula: see text] or placebo ingestion to assess [Formula: see text] [and plasma nitrite ([Formula: see text])] concentrations. Additionally, basal plasma and muscle [Formula: see text] concentrations were assessed in 10 healthy young (CON-Y; age 21 ± 1 yr) and 10 healthy older (CON-O; age 75 ± 1 yr) control subjects. In all groups, baseline [Formula: see text] concentrations were higher in muscle (NIT, 57 ± 7; PLA, 61 ± 7; CON-Y, 80 ± 10; CON-O, 54 ± 6 µmol/l) than in plasma (NIT, 35 ± 3; PLA, 32 ± 3; CON-Y, 38 ± 3; CON-O, 33 ± 3 µmol/l; P ≤ 0.011). Ingestion of NaNO3 resulted in a sustained increase in plasma [Formula: see text], plasma [Formula: see text], and muscle [Formula: see text] concentrations (up to 185 ± 25 µmol/l) in the NIT group (time effect P < 0.001) compared with PLA (treatment effect P < 0.05). In conclusion, basal [Formula: see text] concentrations are substantially higher in human skeletal muscle tissue compared with plasma. Ingestion of a bolus of dietary [Formula: see text] increases both plasma and muscle [Formula: see text] contents in humans. NEW & NOTEWORTHY Literature of the pharmacokinetics following dietary nitrate ingestion is usually limited to the changes observed in plasma nitrate and nitrite concentrations. The present investigation assessed the skeletal muscle nitrate content in humans during the postabsorptive state, as well as following dietary nitrate ingestion. We show that basal nitrate content is higher in skeletal muscle tissue than in plasma and that ingestion of a dietary nitrate bolus strongly increases both plasma and muscle nitrate concentrations.

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Differential patterns of transcript accumulation during human myogenesis

Molecular and Cellular Biology ◽

10.1128/mcb.7.11.4100-4114.1987 ◽

1987 ◽

Vol 7 (11) ◽

pp. 4100-4114

Author(s):

P Gunning ◽

E Hardeman ◽

R Wade ◽

P Ponte ◽

W Bains ◽

...

Keyword(s):

Skeletal Muscle ◽

Carbonic Anhydrase ◽

Myosin Heavy Chain ◽

Heavy Chain ◽

Time Course ◽

Human Skeletal Muscle ◽

Transcript Accumulation ◽

Mrna Accumulation ◽

Adult Human ◽

Alpha Actin

We evaluated the extent to which muscle-specific genes display identical patterns of mRNA accumulation during human myogenesis. Cloned satellite cells isolated from adult human skeletal muscle were expanded in culture, and RNA was isolated from low- and high-confluence cells and from fusing cultures over a 15-day time course. The accumulation of over 20 different transcripts was compared in these samples with that in fetal and adult human skeletal muscle. The expression of carbonic anhydrase 3, myoglobin, HSP83, and mRNAs encoding eight unknown proteins were examined in human myogenic cultures. In general, the expression of most of the mRNAs was induced after fusion to form myotubes. However, several exceptions, including carbonic anhydrase and myoglobin, showed no detectable expression in early myotubes. Comparison of all transcripts demonstrated little, if any, identity of mRNA accumulation patterns. Similar variability was also seen for mRNAs which were also expressed in nonmuscle cells. Accumulation of mRNAs encoding alpha-skeletal, alpha-cardiac, beta- and gamma-actin, total myosin heavy chain, and alpha- and beta-tubulin also displayed discordant regulation, which has important implications for sarcomere assembly. Cardiac actin was the only muscle-specific transcript that was detected in low-confluency cells and was the major alpha-actin mRNA at all times in fusing cultures. Skeletal actin was transiently induced in fusing cultures and then reduced by an order of magnitude. Total myosin heavy-chain mRNA accumulation lagged behind that of alpha-actin. Whereas beta- and gamma-actin displayed a sharp decrease after initiation of fusion and thereafter did not change, alpha- and beta-tubulin were transiently induced to a high level during the time course in culture. We conclude that each gene may have its own unique determinants of transcript accumulation and that the phenotype of a muscle may not be determined so much by which genes are active or silent but rather by the extent to which their transcript levels are modulated. Finally, we observed that patterns of transcript accumulation established within the myotube cultures were consistent with the hypothesis that myoblasts isolated from adult tissue recapitulate a myogenic developmental program. However, we also detected a transient appearance of adult skeletal muscle-specific transcripts in high-confluence myoblast cultures. This indicates that the initial differentiation of these myoblasts may reflect a more complex process than simple recapitulation of development.

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Dietary Nitrate Enhances the Contractile Properties of Human Skeletal Muscle

Exercise and Sport Sciences Reviews ◽

10.1249/jes.0000000000000167 ◽

2018 ◽

Vol 46 (4) ◽

pp. 254-261 ◽

Cited By ~ 20

Author(s):

Andrew R. Coggan ◽

Linda R. Peterson

Keyword(s):

Skeletal Muscle ◽

Human Skeletal Muscle ◽

Contractile Properties ◽

Dietary Nitrate

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Time Course Analysis Reveals Gene-Specific Transcript and Protein Kinetics of Adaptation to Short-Term Aerobic Exercise Training in Human Skeletal Muscle

PLoS ONE ◽

10.1371/journal.pone.0074098 ◽

2013 ◽

Vol 8 (9) ◽

pp. e74098 ◽

Cited By ~ 61

Author(s):

Brendan Egan ◽

Paul L. O’Connor ◽

Juleen R. Zierath ◽

Donal J. O’Gorman

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Aerobic Exercise ◽

Time Course ◽

Human Skeletal Muscle ◽

Aerobic Exercise Training ◽

Short Term ◽

Protein Kinetics ◽

Specific Transcript ◽

Kinetics Of

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Increments in skeletal muscle GLUT-1 and GLUT-4 after endurance training in humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.270.3.e456 ◽

1996 ◽

Vol 270 (3) ◽

pp. E456-E462 ◽

Cited By ~ 17

Author(s):

S. M. Phillips ◽

X. X. Han ◽

H. J. Green ◽

A. Bonen

Keyword(s):

Skeletal Muscle ◽

Time Course ◽

Human Skeletal Muscle ◽

Prolonged Exercise ◽

Mitochondrial Potential ◽

Glut 1 ◽

Glut 4 ◽

Induced Changes ◽

Muscle Biopsies ◽

Early Training

We investigated the time course of training-induced changes in the expression of GLUT-1 and GLUT-4 in human skeletal muscle. Seven healthy males trained for 2 h/day (approximately 60% pretraining VO2peak) for 31 days (31D). Muscle biopsies were obtained before training (PRE) and after 5 (5D) and 31 days (31D) of training. Training resulted in progressive increases in muscle GLUT-4 with increasing training duration (PRE<5D<31D; P<0.01). Muscle GLUT-1 content was also increased (P<0.05) after training; however, the increase was not observed until 31D (131%). Increases in muscle hexokinase (HK) activity were complete by 5D (P<0.01). Muscle malate dehydrogenase activity was not elevated after 5D of training but was increased (+35%; P<0.01) at 31D. Results from this study show that increases in both GLUT-4 and HK represent early training-induced adaptations to prolonged exercise training. As training progresses, further increases in GLUT-4, but not HK, occur in conjunction with an increase in muscle mitochondrial potential and GLUT-1.

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2-D DIGE analysis of the mitochondrial proteome from human skeletal muscle reveals time course-dependent remodelling in response to 14 consecutive days of endurance exercise training

PROTEOMICS ◽

10.1002/pmic.201000597 ◽

2011 ◽

Vol 11 (8) ◽

pp. 1413-1428 ◽

Cited By ~ 43

Author(s):

Brendan Egan ◽

Paul Dowling ◽

Paul L. O'Connor ◽

Michael Henry ◽

Paula Meleady ◽

...

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Endurance Exercise ◽

Time Course ◽

Human Skeletal Muscle ◽

Mitochondrial Proteome ◽

Endurance Exercise Training ◽

Dige Analysis

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TWEAK-Fn14 pathway activation after exercise in human skeletal muscle: insights from two exercise modes and a time course investigation

Journal of Applied Physiology ◽

10.1152/japplphysiol.00759.2014 ◽

2015 ◽

Vol 118 (5) ◽

pp. 569-578 ◽

Cited By ~ 18

Author(s):

Ulrika Raue ◽

Bozena Jemiolo ◽

Yifan Yang ◽

Scott Trappe

Keyword(s):

Skeletal Muscle ◽

Protein Expression ◽

Time Course ◽

Human Skeletal Muscle ◽

Vastus Lateralis ◽

Cell Surface Receptor ◽

Vastus Lateralis Muscle ◽

Exercise Mode ◽

Gene And Protein Expression ◽

Surface Receptor

The cell surface receptor Fn14/TWEAKR was recently reported by our laboratory to be a prominent marker in the resistance exercise (RE) induced Transcriptome. The purpose of the present study was to extend our Transcriptome findings and investigate the gene and protein expression time course of markers in the TWEAK-Fn14 pathway following RE or run exercise (RUN). Vastus lateralis muscle biopsies were obtained from 6 RE subjects [25 ± 4 yr, 1-repetition maximum (RM): 99 ± 27 kg] pre- and 0, 1, 2, 4, 8, 12, and 24 h post RE (3 × 10 at 70% 1-RM). Lateral gastrocnemius biopsies were obtained from 6 RUN subjects [25 ± 4 yr, maximum oxygen uptake (V̇o2max): 63 ± 8 ml·kg−1·min−1] pre- and 0, 1, 2, 4, 8, 12, and 24 h after a 30-min RUN (75% V̇o2max). After RE, Fn14 gene and protein expression were induced ( P < 0.05) and peaked at 8 and 12 h, respectively. Downstream markers analyzed showed evidence of TWEAK-Fn14 signaling through the alternative NF-κB pathway after RE. After RUN, Fn14 gene expression was induced ( P < 0.05) to a much lesser extent and peaked at 24 h. Fn14 protein expression was only measurable on a sporadic basis, and there was weak evidence of alternative NF-κB pathway signaling after RUN. TWEAK gene and protein expression were not influenced by either exercise mode. These are the first human data to show a transient activation of the TWEAK-Fn14 axis in the recovery from exercise, and our data suggest the level of activation is exercise mode dependent. Furthermore, our collective data support a myogenic role for TWEAK-Fn14 through the alternative NF-κB pathway in human skeletal muscle.

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Rapid vasoregulatory mechanisms in exercising human skeletal muscle: dynamic response to repeated changes in contraction intensity

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00368.2006 ◽

2006 ◽

Vol 291 (3) ◽

pp. H1065-H1073 ◽

Cited By ~ 12

Author(s):

Anna M. Rogers ◽

Natasha R. Saunders ◽

Kyra E. Pyke ◽

Michael E. Tschakovsky

Keyword(s):

Skeletal Muscle ◽

Heart Rate ◽

Blood Flow ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Exercise Intensity ◽

Time Course ◽

Human Skeletal Muscle ◽

Muscle Blood Flow ◽

Relaxation Phase

We tested the hypothesis that vasoregulatory mechanisms exist in humans that can rapidly adjust muscle blood flow to repeated increases and decreases in exercise intensity. Six men and seven women (age, 24.4 ± 1.3 yr) performed continuous dynamic forearm handgrip contractions (1- to 2-s contraction-to-relaxation duty cycle) during repeated step increases and decreases in contraction intensity. Three step change oscillation protocols were examined: Slow (7 contractions per contraction intensity × 10 steps); Fast (2 contractions per contraction intensity × 15 steps); and Very Fast (1 contraction per contraction intensity × 15 steps). Forearm blood flow (FBF; Doppler and echo ultrasonography), heart rate (ECG), and mean arterial pressure (arterial tonometry) were examined for the equivalent of a cardiac cycle during each relaxation phase (FBFrelax). Mean arterial pressure and heart rate did not change during repeated step changes ( P = 0.352 and P = 0.190). For both Slow and Fast conditions, relaxation phase FBFrelax adjusted immediately and repeatedly to both increases and decreases in contraction intensity, and the magnitude and time course of FBFrelax changes were virtually identical. For the Very Fast condition, FBFrelax increased with the first contraction and thereafter slowly increased over the course of repeated contraction intensity oscillations. We conclude that vasoregulatory mechanisms exist in human skeletal muscle that are capable of rapidly and repeatedly adjusting muscle blood flow with ongoing step changes in contraction intensity. Importantly, they demonstrate symmetry in response magnitude and time course with increasing versus decreasing contraction intensity but cannot adjust to very fast exercise intensity oscillations.

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