J. Appl. Physiol. [JOURNAL]
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200 papers
Motor unit adaptations contribute to the repeated bout effect following damaging resistance exercise.
Hayman O, Ansdell P, Angius L … +6 more , Thomas K, Howatson G, Kidgell DJ, Škarabot J, Martinez-Valdes E, Goodall S
J Appl Physiol (1985) · 2026 Feb · PMID 41553735 · Publisher ↗
An initial bout of eccentric exercise (EE) is known to protect against exercise-induced muscle damage (EIMD) following the performance of a subsequent bout of similar volume and intensity, a phenomenon known as the repea...
An initial bout of eccentric exercise (EE) is known to protect against exercise-induced muscle damage (EIMD) following the performance of a subsequent bout of similar volume and intensity, a phenomenon known as the repeated bout effect (RBE). We examined whether aspects of motor unit (MU) behavior and reticulospinal tract (RST) drive are neural components of this protective effect. Twenty-three participants (6 females; age 26 ± 5 yr) performed two bouts of EE (10 repetitions × 10 sets) with the dorsiflexors separated by 3 wk. Maximal voluntary isometric torque (MVIC), muscle soreness (DOMS), MU behavior (quantified from MUs identified via high-density electromyography decomposition), and RST drive (visual-auditory vs. visual-startle reaction time) were recorded at baseline, 24, 48, and 72 h postexercise. Symptoms of EIMD were elevated following ; MVIC was reduced, and perceived soreness was increased. Despite comparable work performed (∼1,300 J; = 0.721), MVIC ( < 0.001) and soreness ( < 0.001) recovered quicker following . The attenuated symptoms of EIMD were coupled with reduced variability in MU discharge rate ( = 0.001) and torque ( < 0.001). MU adjustments were not accompanied by any change in RST drive (-8 ms; = 0.634). Lower MU discharge variability and an attenuated increase in firing rate in support a neural contribution to the RBE. The present study cannot infer whether such adaptations actively protect against muscle damage or merely reflect the reduced mechanical and nociceptive disturbance. Nonetheless, we confirm that MU adjustments are involved in the RBE phenomenon. Unfamiliar eccentric exercise causes muscle damage, but repeating the same exercise later substantially reduces symptoms-an adaptive phenomenon known as the repeated bout effect (RBE). We investigated the neural contributions to this response. We observed lower motor unit discharge variability and smaller increases in firing rate after the repeated bout. These findings provide evidence that motor unit-level neural adjustments are a critical component of the RBE, offering a new perspective on this protective adaptation.
Older adults produce joint moments less economically than young adults.
Alanis B, Fallah N, Mistry A … +1 more , Beck ON
J Appl Physiol (1985) · 2026 Feb · PMID 41546871 · Publisher ↗
Older adults expend more metabolic energy than young adults during walking (worse walking economy). Amid the numerous physiological changes that accompany advanced aging, the mechanisms governing the age-related decline...
Older adults expend more metabolic energy than young adults during walking (worse walking economy). Amid the numerous physiological changes that accompany advanced aging, the mechanisms governing the age-related decline in walking economy remain unestablished. Due to conflicting evidence, we studied whether older adults produce lower-limb joint moments less economically than young adults, independent of an age-related difference in muscle coactivation. Eight older adults (71.6 ± 6.0 yr) and 13 young adults (23.1 ± 4.7 yr) repeatedly produced hip and ankle moment cycles on a dynamometer following visual feedback and an audible metronome. We instructed participants to produce moments with peak net torque values of 20 and 30 Nm at a 0.75 Hz cycle frequency and a 0.5 duty cycle. Overall, young and older adults did not coactivate their antagonist muscles differently during the moment production trials. At the hip, older adults expended more metabolic power than young adults despite producing lower moment amplitudes. At the ankle, older adults expended more metabolic power than young adults while producing nondifferent moment production cycles. Because older adults produced lower-limb joint moments less economically than young adults, interventions aimed at prolonging youthful walking economy into advanced age may need to directly address changing muscle-tendon unit physiology. The mechanisms governing the age-related decline in walking economy are elusive. Here, we demonstrate that older adults produce lower-limb joint moment profiles less economically than young adults. Therefore, less economical muscle-tendon unit force production in older versus young adults likely contributes to their greater metabolic energy expenditure during walking.
Ventricular-arterial coupling in community-dwelling individuals and athletes with cervical spinal cord injury.
Alanis GA, Williams AM, Hayes B … +7 more , Gee CM, Erskine E, Fossey MPM, Poormasjedi-Meibod MS, Sheel AW, Phillips AA, West CR
J Appl Physiol (1985) · 2026 Feb · PMID 41546613 · Publisher ↗
Cervical spinal cord injury (SCI) removes descending sympathetic control over the heart and vasculature, which alters cardiovascular function. Ventricular-arterial coupling (VAC) provides insight into the heart's mechani...
Cervical spinal cord injury (SCI) removes descending sympathetic control over the heart and vasculature, which alters cardiovascular function. Ventricular-arterial coupling (VAC) provides insight into the heart's mechanical and energetic efficiency by evaluating the interaction between cardiac contractility (end-systolic elastance; Ees) and arterial elastance (Ea). This study investigated VAC in nonathletes (SCI-NA) and athletes (SCI-A) with cervical SCI, and able-bodied (AB) controls. We additionally validated noninvasive estimation of Ees with catheter-derived assessments in rodents with SCI. Data were collected on SCI-NA (9 M, 2 F), SCI-A (12 M, 2 F), and AB (10 M, 5 F) individuals. Cardiac contractility was estimated using single-beat Ees and an alternative assessment of contractility derived from the left ventricle outflow tract [contractility]. Ea was determined with the standard Simpson's biplane method [Ea] and with Doppler [Ea]. VAC was determined for each method as: VAC = Ea/Ees and VAC = Ea/contractility. Associations between contractility and catheter Ees in rats were assessed with linear regression and intraclass correlation coefficient (ICC). Compared with AB, contractility was lower in SCI-NA ( < 0.001) and SCI-A ( = 0.04). Ea was higher in SCI-NA versus SCI-A and AB (all < 0.01). As such, SCI-NA exhibited a higher VAC versus AB ( < 0.001) and SCI-A ( = 0.002). In rodents, we found excellent agreement between contractility and Ees (ICC 0.880; = 0.002). SCI-NA exhibit an elevated VAC due to lower contractility and higher Ea, suggesting an uncoupling of the heart and vasculature. SCI-A exhibit preserved VAC despite a lower contractility than AB, suggesting that chronic exposure to exercise maintains coupling between the heart and vasculature. The present study provides the first demonstration that VAC is impaired in humans with SCI, which may further contribute to the poor exercise tolerance often observed in this population. Our findings in the SCI-A group imply that chronic exposure to exercise increases VAC, suggesting that adherence to a long-term exercise program may optimize ventricular-vascular interaction postinjury.
Acute changes in motor unit behavior to fatiguing isometric contractions with blood flow restriction in healthy individuals.
Angius L, Hayman O, Durbaba R … +2 more , Howatson G, Goodall S
J Appl Physiol (1985) · 2026 Feb · PMID 41543359 · Publisher ↗
Fatiguing contractions performed with limited oxygen supply develop a higher neuromuscular fatigue, perceived effort, and muscle pain that reduce exercise capacity. Despite these consistent observations, there is limited...
Fatiguing contractions performed with limited oxygen supply develop a higher neuromuscular fatigue, perceived effort, and muscle pain that reduce exercise capacity. Despite these consistent observations, there is limited information about motor unit (MU) behavior in response to limited oxygen supply. Fourteen healthy participants (means ± SD age, 29 ± 5 yr; height, 175 ± 7 cm; mass, 75 ± 11.1 kg) were recruited. Neuromuscular function, perceived effort, muscle pain, and MU behavior were monitored during isometric contractions of the dominant ankle dorsiflexors at 60% of maximal voluntary contraction (MVC), with blood flow restriction (BFR) and without (Control). High-density surface electromyography was used to investigate MU behavior of the tibialis anterior muscle. MU were tracked across contractions and classified as relatively lower-threshold (≤30% MVC) and higher-threshold (> 30% MVC). During exercise with BFR, heart rate, perceived effort, and muscle pain were higher ( < 0.001). BFR induced greater neuromuscular fatigue, reduced maximal muscle activation, and muscle contractile function ( < 0.001). The discharge rate of lower-threshold MU decreased ( < 0.001), whereas it increased for higher-threshold MU ( ≤ 0.003). Both MU types exhibited reduced recruitment and derecruitment thresholds with BFR ( < 0.001). These results show disparate adjustment between lower- and higher-threshold MU during exercise with limited oxygen supply. Higher discharge rate of relatively higher-threshold MU might be required to compensate for the lower discharge rate of relatively lower-threshold MU. This suggests that the nervous system adopts an acute neural strategy to maintain force production during contractions with limited oxygen supply. The behavior of motor units during high-intensity fatiguing contractions with limited oxygen supply is poorly investigated. Here, we show that during fatiguing exercise with blood flow restriction, motor units are recruited at lower force levels with inhibition of relatively lower-threshold motor units and increased activity of relatively higher-threshold motor units. These changes in motor unit behavior might represent an acute neural adaptation to produce force during high-intensity contractions with limited oxygen supply.
The modulation of human motoneuron discharge patterns with contraction force in resistance- and endurance-trained individuals.
Škarabot J, Thomason H, Nazaroff BM … +6 more , Connelly CD, Valenčič T, Ho ML, Tyagi K, Beauchamp JA, Pearcey GEP
J Appl Physiol (1985) · 2026 Feb · PMID 41533434 · Full text
Motoneurons adapt to both resistance and endurance training in reduced animal preparations, with adaptations seemingly more apparent in higher-threshold neurons, but similar evidence in humans is lacking. We compared ide...
Motoneurons adapt to both resistance and endurance training in reduced animal preparations, with adaptations seemingly more apparent in higher-threshold neurons, but similar evidence in humans is lacking. We compared identified motor unit (MU) discharge patterns from decomposed electromyography signals acquired during triangular dorsiflexion contractions up to 70% of maximal voluntary force (MVF) between resistance-trained, endurance-trained, and untrained individuals ( = 23 per group). We estimated the contribution of intrinsic motoneuron properties and the proportion of excitatory, inhibitory, and neuromodulatory inputs to motoneuron discharge across contraction intensities in each group. Participants also performed a "sombrero" task (triangular contractions superimposed onto sustained ones) designed to challenge inhibitory control of dendritic persistent inward currents (PICs). Both trained groups demonstrated higher MU discharge rates with greater ascending discharge rate modulation during higher contraction forces (≥50% MVF), which were accompanied by more linear MU discharge patterns with steeper slopes after PIC-induced acceleration. The lack of differences in discharge rate hysteresis (triangular contractions) and the discharge rate characteristics during sombrero contractions suggests that neuromodulatory input is not different between groups. Conversely, since resistance-compared with endurance-trained individuals exhibited steeper PIC-induced acceleration during lower contraction forces (≤50% MVF), there is a possibility of enhanced PIC activation at onset. Collectively, the greater discharge rates and more linear but steeper MU discharge patterns in the trained groups suggest a more reciprocal (i.e., push-pull) excitation-inhibition coupling during higher contraction forces, leading to enhanced net excitatory synaptic input to the motor pool, which might underpin greater force production of trained individuals. Physical training alters intrinsic motoneuron properties in reduced animal preparations, especially in neurons recruited at high excitation levels. Here, we show that individuals with a history of resistance or endurance training exhibit higher discharge rates that are more linear during forceful contractions. This likely reflects a more reciprocal/push-pull excitation-inhibition coupling, leading to greater net excitation to the motor pool that may contribute to greater force production observed in trained individuals.
Changes in pulmonary function and airway mechanics with increased serum osmolality.
Gideon EA, Hubbard CD, Hite MJ … +3 more , Schlader ZJ, Duke JW, Cross TJ
J Appl Physiol (1985) · 2026 Feb · PMID 41533428 · Publisher ↗
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 osm...
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 ( = 7) and women ( = 7) with an exploratory comparison between sexes. We found that the hypertonic saline infusion significantly increased serum osmolality (287 ± 3 vs. 311 ± 17 mosmol/kgHO; < 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; = 0.002-0.02) with no effect of sex ( = 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 ( = 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. 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.
Standard V̇o measures underestimate metabolic demand during blood flow-restricted exercise.
Bendell AM, McCarthy DG, Burr JF
J Appl Physiol (1985) · 2026 Feb · PMID 41525157 · Publisher ↗
Systemic oxygen consumption (V̇o) 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 (BF...
Systemic oxygen consumption (V̇o) 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), V̇o may no longer reflect metabolic cost. The purpose of this study was to evaluate the total oxygen requirement (Vo) of walking with and without BFR, including in-exercise Vo 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 Vo was initially lower in the BFR condition compared with control (CON) ( = 0.0002), but reversed over time, with BFR producing a greater total walking Vo (BFR: 16,638 ± 2,157 mL; CON: 15,219 ± 2,444 mL; = 0.0006) and higher EPOC (BFR: 7,789 ± 837 mL; CON: 6,267 ± 1,102 mL; < 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%; = 0.0012), together indicating a time-dependent shift in V̇o. This suggests that acute, rate-based V̇o 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. This study challenges the reliability of V̇o as a standalone marker of metabolic demand during blood flow-restricted (BFR) exercise. Although V̇o 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.
Misconceptions about variance comparisons for exploring the presence of treatment response heterogeneity in randomized controlled trials.
Atkinson G, Lolli L, Batterham AM
J Appl Physiol (1985) · 2026 Jan · PMID 41505717 · Publisher ↗
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Neonatal inflammation induces lasting sex- and region-dependent microglia activation and sex-dependent impairments in chemoreflexes.
Beyeler SA, Plunkett DLM, Watters JJ … +1 more , Huxtable AG
J Appl Physiol (1985) · 2026 Feb · PMID 41500514 · Full text
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...
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. 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.
Plasma heat shock protein-70 response to acute prolonged exercise: a systematic review, meta-analysis, and meta-regression.
Charoensap T, Kilding AE, Barrett AMS … +3 more , Cross MR, Stewart T, Maunder E
J Appl Physiol (1985) · 2026 Feb · PMID 41494650 · Publisher ↗
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 r...
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. 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, 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, 95% CI [0.13, 1.34], = 0.02). Meta-regression explained ∼57.1% of variation in exercise-induced change in plasma HSP70 concentration (marginal = 0.571). The V̇o (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.
Differences in persistent inward current contribution to spinal motor neuron behavior between early morning and late afternoon.
Bontemps B, Cattagni T, Avrillon S … +1 more , Hug F
J Appl Physiol (1985) · 2026 Feb · PMID 41494641 · Publisher ↗
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 varie...
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: ) a relative condition, where the target force corresponded to 40% of the maximal voluntary force (MVF) measured during that session, and ) 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 Δ, 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 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. 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.
Acute effects of passive stretching on skeletal muscle microvascular Po and HIF-1α expression: influence of stretch intensity and duration.
Kataoka R, Hotta K, Kurosaki Y … +7 more , Ishii N, Izawa K, Fukuzaki N, Arai S, Kamiya K, Muller-Delp J, Matsunaga A
J Appl Physiol (1985) · 2026 Feb · PMID 41467762 · Publisher ↗
This study investigated the acute effects of passive stretching on microvascular oxygen partial pressure ([Formula: see text]) and hypoxia-inducible factor-1α (HIF-1α) expression in rat skeletal muscle, focusing on stret...
This study investigated the acute effects of passive stretching on microvascular oxygen partial pressure ([Formula: see text]) and hypoxia-inducible factor-1α (HIF-1α) expression in rat skeletal muscle, focusing on stretch intensity and duration. Twenty male Wistar rats were assigned to either a stretch or sham group. In , the soleus muscle was passively stretched at varying intensities by changing its length from the optimal length (L) by 2, 4, 6, 8, and 10 mm, whereas [Formula: see text] was simultaneously measured. In a separate experiment, the muscle was stretched from L to 8 mm and maintained in the stretched position for 2 h, whereas in the sham group it was kept at L throughout. After stretching, the muscle was rapidly frozen, and HIF-1α mRNA was quantified by real-time PCR. Passive stretching induced an acute, intensity-dependent decrease in [Formula: see text]. Values during high-intensity stretches (6-10 mm) were significantly lower than in the sham group (25 ± 9 vs. 39 ± 7 mmHg, 8 mm vs. L; < 0.05). Sustained 8 mm stretching caused a rapid decline in [Formula: see text] within 40 s, followed by a stable low plateau for 2 h (time = 11.2; group = 17.9; interaction = 2.10; < 0.01). Interestingly, 2 h of stretching reduced HIF-1α mRNA expression. These findings demonstrate that passive stretching elicits an intensity-dependent and sustained reduction in microvascular Po, which may suppress HIF-1α mRNA expression in skeletal muscle. The intramuscular oxygen dynamics during stretching remain unclear. Real-time changes in Po during passive stretching were investigated using phosphorescence quenching. Microvascular Po decreased in an intensity-dependent manner and remained low during prolonged stretching. The decline reached a plateau about 2 min after stretch onset. Moreover, 2 h of sustained stretching downregulated HIF-1α mRNA. Collectively, these findings indicate that passive stretching induces acute, intensity-dependent microvascular hypoxia that persists and alters hypoxia-related transcriptional responses in skeletal muscle.
The impact of biological sex and female sex hormone concentration on the maximal metabolic steady state.
Schoeberlein MI, Hudgins JH, DeVelasco O … +1 more , Wilkins BW
J Appl Physiol (1985) · 2026 Feb · PMID 41460237 · Publisher ↗
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 stead...
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 48.1 ± 5.2 vs. 57.3 ± 5.3 mL·min·kg; = 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 (%SmO) zero-slope prediction cycling protocol once a week for 4 wk. The %SmO 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 %SmO 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 ( < 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) ( = 0.224) nor across the four visits ( = 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. 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.
Estrogen receptor signaling markers are poor predictors of muscle hypertrophy outcomes in young women and men.
Bergamasco JGA, Scarpelli MC, Godwin JS … +11 more , Mesquita PHC, Chaves TS, Silva DG, Bittencourt D, Dias NF, Medalha RA, Angleri V, Kavazis AN, Ugrinowitsch C, Roberts MD, Libardi CA
J Appl Physiol (1985) · 2026 Feb · PMID 41460218 · Publisher ↗
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) prot...
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. 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.
Ingesting menthol in a beverage may alter the sweating response during passive heat stress, but only when the beverage is cold.
Nelson M, Lefebvre K, Newhouse D … +2 more , Foster F, Ravanelli N
J Appl Physiol (1985) · 2026 Feb · PMID 41455112 · Publisher ↗
Consuming cold fluids during heat stress can alter sweating responses; however, it remains unclear why chemical activation of cold-sensitive transient receptor potential melastatin 8 (TRPM8) with menthol only induces a c...
Consuming cold fluids during heat stress can alter sweating responses; however, it remains unclear why chemical activation of cold-sensitive transient receptor potential melastatin 8 (TRPM8) with menthol only induces a cold sensation. Animal models propose that complete cold transduction with TRPM8 chemical stimulation must be combined with physical cooling to impact thermoeffector responses. To address this, 12 participants (5 females and 7 males; 22 ± 5 yr; 79.5 ± 15.0 kg; 1.8 ± 0.1 m) conducted four passive heating protocols in random order where, within trial, they consumed 3.2 mL/kg body mass of either ) 37°C water, ) 1.5°C water, ) 37°C menthol solution (0.05%), or ) 1.5°C menthol solution (0.05%); 5 min before heating, and following a 0.5°C and 1.0°C increase in rectal temperature. Forearm sweating onset was attenuated with 1.5°C compared with 37°C (+0.16°C, = 0.001) and delayed with menthol (+0.15°C, = 0.03), but not at the forehead (main effect of temperature: +0.08°C, = 0.17, menthol: +0.09°C, = 0.17). Sudomotor thermosensitivity at the forearm and forehead was attenuated with 1.5°C compared with 37°C (-0.62 mg/cm/min/°C, = 0.02) but not affected by menthol (-0.11 mg/cm/min/°C, = 0.55). A small attenuation in forearm (-0.05 mg/cm/min) and forehead (-0.08 mg/cm/min) sweat rate was observed with 1.5°C combined with menthol, following a 0.5°C ( < 0.04), but not a 1.0°C ( > 0.09) rise in rectal temperature; 1.5°C water alone, nor 37°C water with or without menthol, altered sweating during passive heat stress ( ≥ 0.55). Collectively, chemical stimulation of TRPM8 within the gastrointestinal tract could alter thermoregulatory sweating, but only when paired with physical cooling, and the effect is small. Chemical stimulation of TRPM8 channels during heat stress provides alterations in thermal perception without impacting sweating. However, evidence to date in humans has not considered the impact of fluid temperature, which may be needed to fully induce cold transduction. We provide evidence that coadministration of a TRPM8 agonist with physical cold stimulation is required to alter sudomotor output during heat stress; however, this effect is small.
Hot water immersion: a (not so) new therapy for the primary and secondary prevention of hypertension?
Roxburgh BH, Cotter JD, Fujii N … +2 more , Masodsai K, Thomas KN
J Appl Physiol (1985) · 2026 Feb · PMID 41455109 · Publisher ↗
Hypertension affects over 30% of adults worldwide, significantly increasing the risk of cardiovascular, cerebrovascular, and renal diseases. Although regular physical activity is a well-established strategy for lowering...
Hypertension affects over 30% of adults worldwide, significantly increasing the risk of cardiovascular, cerebrovascular, and renal diseases. Although regular physical activity is a well-established strategy for lowering blood pressure, additional therapeutic approaches may help individuals who struggle to achieve target blood pressure levels. Hot water immersion is garnering attention due to its potential cardiovascular benefits. Historically practiced for therapeutic and cultural purposes, hot water immersion induces physiological responses that share key similarities with physical activity. Accumulating evidence suggests that hot water immersion may contribute to blood pressure reduction. Although small-scale studies report promising acute and chronic blood-pressure-lowering effects, critical gaps remain in the literature. This review summarizes current evidence on the antihypertensive effects of hot water immersion, outlining key areas for future research. Hot water immersion may emerge as an accessible and culturally relevant adjunct therapy for hypertension management.
One night at 1,900 m prompts ventilatory acclimatization without altering cardiac autonomic regulation at 3,000 m in males with coronary artery disease.
Taboni A, Lombardi C, Masè M … +7 more , Roche J, Turner R, Bilo G, Parati G, Strapazzon G, Vinetti G, Gatterer H
J Appl Physiol (1985) · 2026 Feb · PMID 41455100 · Publisher ↗
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 w...
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 CO ([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) than placebo (6 [3, 13] h, = 0.02). At 3,000 m, [Formula: see text] was higher after intervention (88 ± 2%) than placebo (87 ± 2%, = 0.03), [Formula: see text] was lower after intervention (34 ± 3 mmHg) than placebo (36 ± 3 mmHg, = 0.002), cTSI decrease was smaller after intervention (-3.6 ± 2.2%) than placebo (-6.5 ± 3.1%, = 0.02), and PASP was higher after intervention (30 ± 8 mmHg) than after placebo (28 ± 7 mmHg, = 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. 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.
Surfactant therapy for the treatment of acute respiratory distress syndrome: time to revisit?
Lee KG, Greendyk RA, Goligher EC
J Appl Physiol (1985) · 2026 Jan · PMID 41407316 · Full text
Pulmonary surfactant is a vital component of respiratory physiology. Surfactant homeostasis is disrupted in various pulmonary disease states, and exogenous surfactant therapy has been proposed as a treatment to improve l...
Pulmonary surfactant is a vital component of respiratory physiology. Surfactant homeostasis is disrupted in various pulmonary disease states, and exogenous surfactant therapy has been proposed as a treatment to improve lung function and recovery. Although this therapy has demonstrated clinically significant benefit in neonatal respiratory distress syndrome, for adult patients with acute respiratory distress syndrome (ARDS), the evidence is inconclusive. To understand the potential shortcomings of past trials and potential opportunities for more effective exogenous surfactant use in ARDS, we review in detail past trials and literature involving exogenous surfactant therapy in adult patients with ARDS. We assess various factors that may have impacted trial results and propose potential solutions and areas for future research. Advances in surfactant research suggest a potential role for exogenous surfactant therapy for adult patients with ARDS.
Assessing limb conduit artery endothelial function with flow-mediated dilation in response to sustained, exercise-induced increases in shear stress.
Lew LA, McGarity-Shipley EC, Curd ED … +5 more , Ethier TS, Etwaroo R, Sardo C, Vitez ME, Pyke KE
J Appl Physiol (1985) · 2026 Jan · PMID 41397266 · Publisher ↗
Vascular endothelial function can be interrogated by imposing blood flow-associated shear stress, which stimulates endothelial-dependent dilation [flow-mediated dilation (FMD)]. A larger FMD response is indicative of bet...
Vascular endothelial function can be interrogated by imposing blood flow-associated shear stress, which stimulates endothelial-dependent dilation [flow-mediated dilation (FMD)]. A larger FMD response is indicative of better endothelial function. In the well-established technique used to assess human conduit artery endothelial function, a shear stress stimulus is created via the release of temporary limb occlusion, which results in a transient reactive hyperemia (RH; RH-FMD). However, sustained increases in shear stress created with small muscle mass exercise, limb heating or distal vasodilator infusion can also be used to stimulate conduit artery FMD to interrogate endothelial function [sustained stimulus FMD (SS-FMD)]. Cell and animal evidence suggests that endothelial shear stress transduction depends on the duration of the shear stress stimulus such that transient and sustained shear stress exposure recruit distinct signaling pathways. Furthermore, work in humans has demonstrated that RH-FMD and SS-FMD provide unique insight regarding the impact of interventions and clinical conditions on endothelial function. This suggests that testing both RH-FMD and SS-FMD may provide a more comprehensive picture of endothelial function; however, SS-FMD is rarely performed. Here, we describe how SS-FMD can be assessed in the brachial artery using handgrip exercise to achieve either a target shear stress stimulus or an incremental increase in shear stress stimulus. This article provides the first methodological guide to utilize handgrip exercise for assessment of SS-FMD in the brachial artery in response to targeted steady state and incremental increases in shear stress. SS-FMD is a physiologically relevant response, reflecting conduit artery behavior during sustained exertional activity and can provide distinct information regarding endothelial function compared with reactive hyperemia-FMD.
Methodological gaps and conceptual challenges regarding the concept of resilience, durability, fatigability, and repeatability.
Faude O, Ledergerber R, Lichtenstein E
J Appl Physiol (1985) · 2025 Dec · PMID 41396101 · Publisher ↗
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