Journal of applied physiology最新文献

Concurrent training is commonly associated with blunted muscle hypertrophy compared with resistance training alone, but the underlying physiological mechanisms remain unclear. This study aimed to investigate the acute and chronic effects of concurrent versus resistance training on muscle protein synthesis, satellite cell dynamics, myonuclear content, myogenic regulatory factor expression, muscle fiber hypertrophy, strength, and aerobic capacity. Nineteen previously untrained young men were randomly assigned to either concurrent or resistance training for 16 wk. Muscle biopsies were collected before and 48 h after a standardized exercise session at weeks 4 and 16. Samples were analyzed for myofibrillar protein synthesis via deuterium oxide incorporation, satellite cell content, myonuclear number, and gene expression. Strength, aerobic capacity, and muscle fiber cross-sectional area were measured at baseline and postintervention. Muscle protein synthesis increased 48 h postexercise at both weeks 4 and 16 (P = 0.0105), with no group differences. Satellite cell content increased over time in type II fibers only (P = 0.0021). Myonuclear number increased in both fiber types (type I: P = 0.0301 and type II: P = 0.0009), with higher values in type I fibers in the concurrent training group (P = 0.0027). MYF5 and MYF6 expression increased over time (P = 0.0141 and P = 0.034, respectively), and MYOD1 was elevated postexercise only in concurrent training (P = 0.0009). Type II fiber size increased (P = 0.016). Strength gains were greater in resistance training (P = 0.016), whereas aerobic capacity improved only in concurrent training (P < 0.001). Sixteen weeks of concurrent training did not inhibit molecular mechanisms associated with muscle hypertrophy in previously untrained individuals.NEW & NOTEWORTHY Sixteen weeks of concurrent training with long-interval HIIT preserved key molecular adaptations related to muscle hypertrophy, including protein synthesis, satellite cell activity, and gene expression. Both concurrent and resistance training increased type II fiber cross-sectional area, but only concurrent training improved V̇o_2peak. Although strength gains were lower with concurrent training, molecular and cellular remodeling remained intact, supporting it as an effective strategy to enhance both muscle growth and aerobic fitness simultaneously.

The goal was to explore the impact of fluctuating female sex hormone concentrations on the work rate delineating sustainable from unsustainable work rates at the heavy to severe domain boundary or maximal metabolic steady state (MMSS). Thirty endurance-trained participants (15 F/15 M; V̇o_2max 48.1 ± 5.2 vs. 57.3 ± 5.3 mL·min^-1·kg^-1; P = 0.001) completed four MMSS estimation protocols at distinct sex hormone profiles. Serum sex hormone concentrations, specifically estradiol, progesterone, and testosterone, were determined during each study visit. To identify MMSS at each hormone profile, participants completed a muscle oxygenation (%SmO₂) zero-slope prediction cycling protocol once a week for 4 wk. The %SmO₂ zero-slope protocol consisted of four, 4-min stages (2-min rest) spanning intensity domains. The work rate associated with MMSS was determined using linear regression analysis between workload and %SmO₂ signal slope during the final 2 min of each stage. Linear mixed models showed male sex to be a significant predictor of power at MMSS (P < 0.001), but changes in sex hormone concentrations were not associated with changes in MMSS work rate. No sex differences in MMSS were found when normalized to lean body mass (LBM) (P = 0.224) nor across the four visits (P = 0.074). The LBM normalized work rate at MMSS was similar between men and women. Fluctuations in sex hormone profile in women were not associated with differences in the heavy to severe exercise domain boundary, nor were there any observed sex differences across distinct hormone profiles.NEW & NOTEWORTHY Our study examined the effects of fluctuating sex hormone concentration, rather than menstrual cycle phase, on the maximal metabolic steady state in both men and women. In addition to no sex difference, acute fluctuations in hormone concentration do not impact the lean body mass normalized work rate at the heavy to severe domain boundary in women. Direct measures of sex hormones are important to account for the potential impact of these hormones on physiological outcomes.

Several studies have examined the association between resistance training (RT)-induced muscle hypertrophy and androgen signaling in men. However, only one recent study has reported that estrogen receptor alpha (ERα) protein content positively associates with myofiber hypertrophy following RT. Thus, we investigated the acute and chronic effects of RT on skeletal muscle ERα markers in women and men, and whether these outcomes predicted hypertrophic responses. Given the role of ERα in satellite cell (SC) regulation, we also examined fiber type-specific SC content and SC-related proteins [MyoD, myogenin (Myog), cyclin D1 (CycD1)]. Thirty-eight young individuals (19 women) completed 10 wk of RT. Vastus lateralis biopsies and ultrasound-derived muscle cross-sectional area (mCSA) were obtained at baseline, 24 h after the first session (acute, biopsy only), and postintervention (chronic). Total ERα, cytoplasmic ERα (cERα), and nuclear ERα (nERα) protein contents were assessed through Western blotting, ERα DNA-binding activity by an oligo-ELISA kit, and myofiber characteristics using immunohistochemistry. Men showed higher baseline total ERα than women. Both sexes showed acute reductions in cERα, nERα, MyoD, Myog, and CycD1. RT increased type I and II SC content and decreased cERα and CycD1, with no changes in ERα DNA-binding activity. No correlations were observed between ERα markers and hypertrophy in women, whereas in men, an acute reduction in cERα was negatively correlated with chronic mCSA changes. Although we provide further evidence of skeletal muscle ERα markers being responsive to RT, our data suggest that ERα signaling markers may not be a primary driver in RT-induced muscle growth.NEW & NOTEWORTHY This is the first study to evaluate acute and chronic resistance training-induced changes in skeletal muscle estrogen receptor alpha (ERα) signaling and satellite cell (SC) dynamics in women and men. Although ERα content differed between sexes and SC increased with training, ERα markers were not consistently linked to muscle hypertrophy, particularly in women. These findings challenge the presumed role of ERα in hypertrophic adaptation and provide new insights into sex-specific mechanisms of muscle remodeling.

Systemic oxygen consumption (V̇o₂) has traditionally been the gold standard for assessing aerobic metabolic demand. However, under conditions that alter normal blood flow or ventilation, such as blood flow restriction (BFR), V̇o₂ may no longer reflect metabolic cost. The purpose of this study was to evaluate the total oxygen requirement (Vo₂) of walking with and without BFR, including in-exercise Vo₂ and excess postexercise oxygen consumption (EPOC). In a randomized crossover design, 18 recreationally active participants completed three, 3-min treadmill walking bouts, each separated by a 1-min standing rest to simulate a typical repeated BFR protocol. In the BFR condition, tourniquets were applied to the upper thighs at 100% of the limb occlusion pressure throughout the interval protocol and removed for 15 min of seated recovery. Expired gasses were recorded continuously. Walking Vo₂ was initially lower in the BFR condition compared with control (CON) (P = 0.0002), but reversed over time, with BFR producing a greater total walking Vo₂ (BFR: 16,638 ± 2,157 mL; CON: 15,219 ± 2,444 mL; P = 0.0006) and higher EPOC (BFR: 7,789 ± 837 mL; CON: 6,267 ± 1,102 mL; P < 0.0001). The relative contribution of EPOC to total oxygen demand was elevated with BFR (BFR: 32.0 ± 2.8%; CON: 29.2 ± 2.1%; P = 0.0012), together indicating a time-dependent shift in V̇o₂. This suggests that acute, rate-based V̇o₂ does not fully capture the true metabolic demands of BFR exercise. Researchers should instead consider the total oxygen and recovery when interpreting metabolic load during BFR.NEW & NOTEWORTHY This study challenges the reliability of V̇o₂ as a standalone marker of metabolic demand during blood flow-restricted (BFR) exercise. Although V̇o₂ during BFR walking was initially lower, a delayed rise during and prolonged recovery following BFR resulted in a greater total oxygen cost and excess postexercise oxygen consumption (EPOC). We suggest a temporal shift of oxygen dynamics, reflecting altered timing of uptake and recovery. Total oxygen uptake should be considered with BFR exercise.

Dehydration and associated increases in plasma osmolality have been shown to decrease pulmonary function. The suggested mechanism is a decline in small airway function and premature airway closure caused by increased osmolality, but this has not been directly tested. The purpose of this study was to measure pulmonary function, closing capacity, and maximal flow-static recoil curves pre- and postinfusion of isotonic and hypertonic saline in men (n = 7) and women (n = 7) with an exploratory comparison between sexes. We found that the hypertonic saline infusion significantly increased serum osmolality (287 ± 3 vs. 311 ± 17 mosmol/kgH₂O; P < 0.001) leading to decreases in forced vital capacity and forced expired volume in 1 s (4.6 ± 1.1 L and 3.9 ± 0.9 L, respectively) compared with preinfusion (4.8 ± 1.1 L and 4.1 ± 0.9 L, respectively; P = 0.002-0.02) with no effect of sex (P = 0.06-0.39). There was a significant main effect of time for residual volume, closing volume, and closing capacity such that following both isotonic and hypertonic saline, these values were increased compared with preinfusion (P = 0.001-0.033). In addition, maximal flow for a given lung recoil pressure was decreased following hypertonic saline infusion. Thus, pulmonary function decreased following increased serum osmolality, and this change may be caused by small airway dysfunction and premature airway compression and closure.NEW & NOTEWORTHY Increased serum osmolality through hypertonic saline infusion leads to a decrease in forced vital capacity and forced expiratory volume in 1 s. This decline in pulmonary function is likely resultant from changes in airway structure and function based on changes in closing capacity and maximal flow-static recoil curves following hypertonic saline infusion.

Neonatal inflammation is common and has lasting detrimental consequences for the health of the adult nervous system, including on the neural control of breathing. Our previous work demonstrated that neonatal inflammation abolished adult respiratory motor plasticity; yet, the mechanisms underlying this impairment or the broader impact of neonatal inflammation on control of breathing were unknown. Since microglia are key immune cells in the brain and contribute to lasting sex-specific disruptions in nonrespiratory behaviors, we hypothesized that neonatal inflammation would induce lasting sex-dependent activation of adult microglia in respiratory control regions and contribute to broader breathing impairments. In support of this hypothesis, neonatal inflammation increased adult male medullary microglia number and TNF-α gene expression. In adult females, microglia number was unchanged, but neonatal inflammation increased female medullary microglial IL-6 gene expression. Surprisingly, changes in adult microglia were confined to the medulla and cortex, with no changes in ventral cervical spinal microglia, suggesting that the origins of impaired respiratory motor plasticity after neonatal inflammation are likely outside the spinal cord. Neonatal inflammation also augmented adult male hypercapnic ventilatory responses and hypoxic ventilatory responses, and decreased sighs in females, consistent with neonatal inflammation increasing adult risks for ventilatory control disorders. Thus, lasting increases in microglia number and inflammatory gene expression likely contribute to abolished adult respiratory motor plasticity after neonatal inflammation, with distinct inflammatory mechanisms likely underlying abolishment in males and females.NEW & NOTEWORTHY Neonatal inflammation is common, yet our understanding of the mechanisms underlying impairment is poorly understood. Here, we demonstrate for the first time that adult medullary microglia sex- and region-specifically contribute to lasting adult inflammation after neonatal inflammation. Sex-specific activation of adult medullary microglia emphasizes that distinct inflammatory mechanisms underlie male versus female impairments in respiratory control after neonatal inflammation. Such lasting microglia activation likely contributes to abolished adult respiratory motor plasticity and chemoreflexes after neonatal inflammation.

Spending a single night at moderate altitude before ascending to high altitude may enhance ventilatory acclimatization but also exacerbate sympathetic activation, a response that should be carefully pondered in persons with coronary artery disease (CAD). Ten males with CAD participated in this randomized placebo-controlled crossover trial in a hypobaric chamber, where they slept either at simulated 1,900 m (intervention) or in control conditions (250 m, placebo) before being decompressed to 3,000 m the following morning. Respiratory polygraphy was performed each night. Peripheral oxygen saturation ([Formula: see text]), end-tidal partial pressure of CO₂ ([Formula: see text]), cerebral tissue oxygen saturation index (cTSI), baroreflex sensitivity (BRS), heart rate variability (HRV), and pulmonary artery systolic pressure (PASP) were recorded during wakeful rest each morning, both before the overnight stay (at 250 m) and after the simulated ascent to 3,000 m. The intervention night was associated with a greater number of apneas/hypopneas (33 [9, 51] h^-1) than placebo (6 [3, 13] h^-1, P = 0.02). At 3,000 m, [Formula: see text] was higher after intervention (88 ± 2%) than placebo (87 ± 2%, P = 0.03), [Formula: see text] was lower after intervention (34 ± 3 mmHg) than placebo (36 ± 3 mmHg, P = 0.002), cTSI decrease was smaller after intervention (-3.6 ± 2.2%) than placebo (-6.5 ± 3.1%, P = 0.02), and PASP was higher after intervention (30 ± 8 mmHg) than after placebo (28 ± 7 mmHg, P = 0.04), whereas BRS and HRV indices showed no differences. We conclude that a single night at 1,900 m is sufficient to trigger measurable ventilatory acclimatization in persons with CAD without altering BRS and HRV at 3,000 m, but likely enhancing pulmonary hypoxic vasoconstriction.NEW & NOTEWORTHY We found that a single night spent at simulated moderate altitude (1,900 m) prompts measurable ventilatory acclimatization when ascending to simulated high altitude (3,000 m) in males with coronary artery disease. We also found that, although sleeping at 1,900 m increases the occurrence of apneas and/or hypopneas, this did not modify heart rate variability and baroreflex sensitivity responses at 3,000 m.

Extracellular heat shock protein 70 (HSP70) acts as a damage-associated molecular pattern, or "danger signal" for the immune system. Acute prolonged exercise evokes various physiological stresses that can stimulate the release of extracellular HSP70. However, exercise-induced extracellular HSP70 responses are inconsistent in human studies. Therefore, the purpose of this meta-analysis and meta-regression was to systematically evaluate the effect of exercise on plasma HSP70 expression and to determine the exercise-associated factors contributing to plasma HSP70 response. Data were extracted from 26 experimental trials from 13 studies, including 154 participants, in which plasma HSP70 was measured before and after prolonged, continuous running or cycling exercise at a fixed intensity relative to V̇o_2max. Meta-analysis was performed to determine the raw mean difference (MD) between post- and pre-exercise HSP70 concentration. Meta-regression was performed to establish the moderating effects of V̇o_2max, exercise intensity, duration, modality, environmental temperature, humidity, and hypoxia on the plasma HSP70 response. There was a significant effect of exercise on plasma HSP70 concentration (MD = 0.73 ng·mL^-1, 95% CI [0.13, 1.34], P = 0.02). Meta-regression explained ∼57.1% of variation in exercise-induced change in plasma HSP70 concentration (marginal R² = 0.571). The V̇o_2max (β = 0.51, 95% CI [0.03, 1.00]), exercise duration (β = 0.43, 95% CI [0.21, 0.65]), intensity (β = 0.40, 95% CI [0.08, 0.73]), and environmental temperature (β = 0.27, 95% CI [0.10, 0.43]) explained variation in the plasma HSP70 response. These data contribute to our understanding of the factors that modulate the plasma HSP70 response to acute prolonged exercise.

Autonomic cardiovascular control is often disrupted following a spinal cord injury (SCI), resulting in impaired autonomic cardiac regulation and hemodynamic instability. A systematic preregistered review following existing guidelines was undertaken to evaluate the effect of exercise training on noninvasive measures of autonomic cardiovascular control, including orthostatic intolerance, blood pressure variability (BPV), baroreflex function, and heart rate variability (HRV) in adults with SCI. Seven databases were searched from inception to October 2025. Experimental studies (randomized controlled trials, nonrandomized controlled trials, or pre-post studies) consisting of exercise interventions of ≥2 wk evaluating measures of orthostatic tolerance, BPV, baroreflex function, and/or HRV in adults (≥18 yr old) with SCI were included. Risk of bias and study quality were assessed. Of 1,208 unique records identified, 16 studies (329 participants) were included: 8 randomized controlled trials, 3 nonrandomized controlled trials, and 5 pre-post studies. Five of seven studies reported no change in orthostatic intolerance following exercise training, whereas three of five studies found no changes in power spectral analysis of BPV. Conversely, all five studies reporting baroreflex outcomes found improved function, with enhanced cardiovagal baroreflex sensitivity or effectiveness index after training. The 13 studies assessing autonomic cardiac control through HRV reported mixed results, irrespective of whether time- or frequency-domain analyses were used. This review provides preliminary evidence that exercise training can improve baroreflex function in adults with SCI. However, current evidence remains inconclusive regarding whether exercise training can improve HRV, BPV, and the ability to tolerate postural stress and thus prevent orthostatic hypotension.

Despite the critical role of persistent inward currents (PICs) in modulating motor neuron output, and thus neuromuscular performance, it remains unknown whether their contribution to motor neuron discharge behavior varies throughout the day. This study aimed to determine whether PIC-related effects on motor neuron activity during submaximal dorsiflexion tasks differ between the early morning and late afternoon. Eighteen healthy adults (4 females; 27.4 ± 5.6 yr) performed triangular isometric contractions at two randomized time-points on separate days: early morning (7:00-8:30 AM) and late afternoon (5:00-7:30 PM). Two conditions were tested: 1) a relative condition, where the target force corresponded to 40% of the maximal voluntary force (MVF) measured during that session, and 2) an absolute condition, where the target force was 40% MVF recorded during the first session. High-density surface electromyography signals were recorded from the tibialis anterior and decomposed into motor unit spike trains. The prolongation effect of PICs, estimated via ΔF, was significantly greater in the late afternoon in both the relative-absolute force conditions. The amplification effect of PICs, estimated by the acceleration phase of the discharge trajectory, was higher in the late afternoon, but only in the relative force condition. Brace height did not differ between morning and afternoon, but attenuation was lower in the late afternoon during the relative force condition. Collectively, these findings suggest a time-of-day modulation of PIC contribution to motor neuron discharge behavior, likely mediated by a change in inhibitory-excitatory balance between early morning and late afternoon rather than by changes in neuromodulatory drive.NEW & NOTEWORTHY Although human neuromuscular performance often peaks in the late afternoon, this pattern may not arise solely from peripheral mechanisms. This study provides evidence for a modulation in the contribution of persistent inward currents (PICs) to motor neuron discharge behavior between early morning and late afternoon. PIC-related estimates indicate a modest enhancement of motor neuron excitability in the late afternoon, likely explained by a change in the inhibitory-excitatory balance rather than by changes in neuromodulatory drive.