Journal of applied physiology最新文献

{"title":"Comparing spontaneous neurovascular and neurohemodynamic sympathetic transduction in response to hypoxia.","authors":"Adina E Draghici, J Andrew Taylor, Jason W Hamner","doi":"10.1152/japplphysiol.00243.2025","DOIUrl":"10.1152/japplphysiol.00243.2025","url":null,"abstract":"<p><p>Assessment of sympathetic transduction into its effects on the cardiovascular system is of great interest in human research. Analysis of sympathetic transduction has been divided into neurovascular and neurohemodynamic, highlighting the sympathetic effect on either regional vascular or systemic pressure responses. This study investigates whether indices of neurovascular transduction are reflected in parallel neurohemodynamic transduction during normoxia and hypoxia, with and without accounting for the confounds of prevailing tachypnea and tachycardia. In this retrospective study in 11 healthy individuals, we measured beat-by-beat blood pressure, multiunit sympathetic nerve activity (MSNA), and popliteal blood flow velocity with normoxia and isocapnic hypoxia (∼80% [Formula: see text]). Neurovascular transduction was indexed by leg vascular conductance and neurohemodynamic transduction by systemic pressure, derived from signal averaging either conductance or pressure over 10 cardiac cycles after a sympathetic burst. Responses were assessed from raw data and data corrected for ventilation and heart rate. Compared with transduction values during normoxia, sympathetic neurovascular transduction was increased (<i>P</i> = 0.001) and neurohemodynamic transduction was greater (<i>P</i> < 0.01) but delayed (<i>P</i> = 0.03) during hypoxia. When accounting for changes in respiration and cardiac interval, the two indices provided conflicting results-sympathetic neurovascular transduction was unaltered by hypoxia; on the contrary, neurohemodynamic transduction remained increased (<i>P</i> < 0.01), but there was no longer a delayed effect. Regardless, despite corrections for confounding effects of tachypnea and tachycardia, neither neurovascular nor neurohemodynamic transduction indices explained the integrated cardiovascular responses to hypoxia.<b>NEW & NOTEWORTHY</b> Spontaneous neurovascular and neurohemodynamic sympathetic transduction can provide conflicting insight into sympathetic effects on regional and systemic hemodynamics. We examined these transduction indices in response to acute hypoxia in healthy individuals, accounting for confounds of tachypnea and tachycardia. Neither transduction measure fully explained the integrated cardiovascular response. Surprisingly, we found a strong linear relation between neurohemodynamic transduction and low-frequency blood pressure variability, suggesting caution should be used when inferring sympathetic control from hemodynamic indices.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"902-908"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of menstrual phase on lower limb microvascular function, ERα, eNOS, and p-eNOS protein in premenopausal females.","authors":"Lindsay A Lew, James P Thoms, Dylan J Hian-Cheong, Emily J Ferguson, Jacob T Bonafiglia, Chris McGlory, Joe Quadrilatero, Brendon J Gurd, Kyra E Pyke","doi":"10.1152/japplphysiol.00848.2024","DOIUrl":"10.1152/japplphysiol.00848.2024","url":null,"abstract":"<p><p>There is variability in the impact of the menstrual phase on microvascular function with some studies reporting an increase from the early follicular (EF) to late follicular (LF) phase. Estradiol (E2) may increase nitric oxide bioavailability and thereby microvascular function through increasing estrogen receptor α (ERα), endothelial nitric oxide synthase (eNOS), and phosphorylated eNOS (p-eNOS) protein. It is unknown whether variability in ERα, eNOS, and p-eNOS protein levels drives menstrual cycle-related changes in microvascular endothelial function. We hypothesized that microvascular function would be positively related to ERα, eNOS, and p-eNOS protein across the menstrual cycle. Premenopausal females (21 ± 3 yr) completed two visits (EF and LF phase) to assess leg microvascular function (<i>n</i> = 23) and protein levels (<i>n</i> = 17). Microvascular function was quantified by passive leg movement hyperemia leg blood flow area under the curve (LBF AUC) and change to peak (LBF Δpeak). eNOS, p-eNOS, and ERα content were quantified from quadricep muscle biopsies. E2 increased from the EF to LF phase (<i>P</i> = 0.002). There were no phase differences in LBF AUC (<i>P</i> = 0.252) and LBF Δpeak (<i>P</i> = 0.477), or eNOS (<i>P</i> = 0.722), p-eNOS (<i>P</i> = 0.079), and ERα (<i>P</i> = 0.182) protein assessed via immunoblotting, or eNOS (<i>P</i> = 0.610) and p-eNOS (<i>P</i> = 0.510) assessed via immunofluorescence. E2, eNOS, and p-eNOS proteins were positively related to microvascular function (<i>P</i> < 0.05). This study does not support a group-level role of the EF to LF menstrual phase transition in influencing leg microvascular function or ERα, eNOS, and p-eNOS protein. Rather, it highlights that individual quantification of E2 and eNOS protein may be more indicative of microvascular function.<b>NEW & NOTEWORTHY</b> This study provides the first parallel assessments of microvascular function and estrogen-related protein content across the early to late follicular phases of the menstrual cycle in humans. Both microvascular function assessed via passive leg movement hyperemia and estrogen-related protein (eNOS, p-eNOS, and ERα) from skeletal muscle biopsies did not differ across phases; however, correlation analysis suggests a mechanistic link between estradiol, eNOS, and p-eNOS protein levels and peripheral microvascular function in premenopausal females.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"875-888"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise with overdressing for heat acclimation: a multilayered approach using biophysical modeling and two randomized crossover trials.","authors":"Andrew M Greenfield, Shaun C Brazelton, Billie K Alba, Phillip O Bodurtha, Karleigh E Bradbury, Aaron R Caldwell, Christopher L Chapman, Nisha Charkoudian, K Riley Connor, Koby Conz, Benjamin A Fry, Gabrielle E W Giersch, David H Gonzalez-Rojas, Molly E Heikkinen, David P Looney, Thomas A Mayer, Kathryn G McCarthy, Adam W Potter, Timothy P Rioux, Roy M Salgado, Afton D Seeley, MariaLena A Shaw, Xiaojiang Xu, Benjamin J Ryan","doi":"10.1152/japplphysiol.00624.2025","DOIUrl":"10.1152/japplphysiol.00624.2025","url":null,"abstract":"<p><p>Individuals who work in the heat, such as military personnel and athletes, are often required to rapidly transition from temperate or cooler climates to hot environments. Thus, acclimation strategies are needed for individuals lacking access to hot weather. We sought to develop and validate a practical exercise with overdressing protocol for heat acclimation. We began by using biophysical modeling to identify a combination of clothing and treadmill exercise (speed/duration) predicted to facilitate appropriate increases in core temperature in a gym-like environment (20°C/50% RH/1 mph wind). We tested this novel protocol (6 mph run for 30 min followed by 3.5 mph walk for 60 min in a standardized overdressing ensemble) against control exercise (shorts/t-shirt) using two randomized crossover trials in fit males and females. In <i>study I</i>, we showed that a single session of exercise with overdressing elicited significantly higher peak core temperature (38.9 ± 0.4 vs. 38.5 ± 0.3°C), skin temperature (35.3 ± 0.6 vs. 32.5 ± 0.7°C), and heart rate (166 ± 20 vs. 147 ± 16 beats/min) compared with control exercise (<i>P</i> < 0.01; <i>n</i> = 15). In <i>study II</i>, we conducted heat stress tests (60 min at 50% maximal oxygen uptake in 40°C/40%RH/3 mph wind in shorts/t-shirt) before and after five sessions of exercise with overdressing or control exercise (<i>n</i> = 12). Five days of exercise with overdressing in a gym-like environment significantly (<i>P</i> < 0.01) lowered resting core temperature (-0.3 ± 0.2°C), peak core temperature (-0.4 ± 0.2°C), skin temperature (-0.5 ± 0.6°C), and heart rate (-11 ± 11 beats/min) during exercise in the heat. These adaptations were superior compared with control exercise (interactions <i>P</i> < 0.05). This practical exercise with overdressing approach effectively induces heat acclimation in fit males and females without requiring hot weather.<b>NEW & NOTEWORTHY</b> We developed a novel exercise with overdressing protocol for heat acclimation and validated it using two randomized crossover trials. Five sessions of exercise with overdressing in a gym-like environment significantly lowered resting core temperature and peak core temperature, skin temperature, and heart rate during exercise in the heat. These adaptations were superior compared with five sessions of control exercise. This practical exercise with overdressing protocol induces heat acclimation without requiring hot weather.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"889-901"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced sleep irregularity does not impact peripheral vascular function before or following total sleep deprivation.","authors":"Gabriel Narvaez, Joaquin U Gonzales","doi":"10.1152/japplphysiol.00392.2025","DOIUrl":"10.1152/japplphysiol.00392.2025","url":null,"abstract":"<p><p>Consistent sleep patterns are associated with better cardiovascular health, whereas sleep loss is known to impair vascular function. This study examined whether consistent sleep could improve vascular function and mitigate the negative effect of 25-h total sleep deprivation. Sixteen healthy adults [10 females, 6 males; 34 ± 9 yr; body mass index (BMI): 25 ± 3 kg/m²] completed a randomized crossover study involving two 12-night sleep conditions, habitual sleep, and a consistent sleep/wake schedule that were separated by a 1- to 2-wk washout. Sleep was tracked via wrist actigraphy. Vascular assessments were conducted after each sleep condition at baseline and after one night of total sleep deprivation. Forearm reactive hyperemia (RH) was measured using venous occlusion plethysmography. Blood pressure responses to static handgrip exercise and postexercise ischemia (PEI) were assessed using finger photoplethysmography. Consistent sleep reduced sleep irregularity (sleep duration standard deviation) as compared with habitual sleep (0.96 ± 0.24 to 0.51 ± 0.24 h, <i>P</i> < 0.0001). Peak RH was unaltered by consistent sleep (main effect for condition: 27 ± 9 to 28 ± 5 mL/100 mL/min, <i>P</i> = 0.53) and sleep deprivation reduced peak RH (main effect for time: 28 ± 7 to 25 ± 8 mL/100 mL/min, <i>P</i> = 0.004) with no interaction present between sleep conditions (<i>P</i> = 0.69). Resting blood pressure and blood pressure reactivity to handgrip exercise and PEI were unchanged by consistent sleep or total sleep deprivation (<i>P</i> > 0.05). These results find that a short-term reduction in sleep irregularity does not improve resting peripheral vascular function or diminish the decrease in peripheral vasodilation following total sleep deprivation.<b>NEW & NOTEWORTHY</b> We examined the effect of a short-term reduction in sleep duration irregularity on peripheral vascular function. Maintaining a consistent sleep schedule reduced sleep duration standard deviation (SD) but had no effect on peak reactive hyperemia in the forearm or blood pressure reactivity to sympathetic stimuli. One night of total sleep deprivation decreased peak reactive hyperemia in the forearm, an impairment that was not mitigated by consistent sleep behavior.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"909-917"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Physiological Study of Radiation-Induced Lung Injury: Effects on Cardiac Function and Kidney Integrity.","authors":"Lucas Rodrigues de Moraes, Maicon Luiz de Lima, Antônio Pedro Abido Ribeiro, Nazareth de Novaes Rocha, Tula Celeste Wilmart Gonçalves, Rodrigo Jorge Vianna Barbosa, Klara de Souza Roque, Giovanna Costa Ferreira Santos, Amanda Pereira da Cruz, Rodrigo Gonzada Veras, Sabrina Araújo Ferreira, Pedro Henrique Lima da Conceição, Raquel Ferreira de Magalhães Sacramento, Adriana Lopes da Silva Vilardo, Vera Luiza Capelozzi, Camila Machado Baldavira, Sarah Aparecida Dos Santos Alves, Fernanda Ferreira Cruz, Patricia Rieken Macedo Rocco, Celso Caruso-Neves, Sergio Augusto Lopes de Souza, Lorenzo Ball, Pedro Leme Silva","doi":"10.1152/japplphysiol.00241.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00241.2025","url":null,"abstract":"<p><p>Radiotherapy is used to treat tumours in the chest, but can cause radiation-induced lung injury (RILI) in 5-50% of patients. The study investigated changes in lung and heart function and kidney integrity in a model of RILI. Primary outcome was lung compliance at 12 weeks. Secondary outcomes included analysis of ventilatory effort, cardiovascular function and renal integrity. 30 adult Wistar rats (8-10 weeks-old, 390±22g) were randomized into two groups: one received 15Gy of irradiation to the right lung (RLR group, n=20), while control group (CTRL group, n=10) received no irradiation. After irradiation, echocardiography and chest computed tomography (CT) were performed every 3 weeks, while respiratory mechanics and right ventricle systolic pressure (RVSP) were assessed at 12 weeks. Lung tissue was analyzed for collagen deposition and immunohistochemistry markers, including signal transducer and activator of transcription-3 (STAT-3) and transforming growth factor-beta (TGF-β). Kidney tissue was evaluated for tubular cell spacing and collagen deposition. In RLR, compared to CTRL group, lung compliance reduced (0.24±0.02 ml.cmH₂O^-1 vs. 0.29±0.03 ml.cmH₂O^-1; p=0.039), while respiratory effort increased. CT analysis demonstrated progressive left lung volume expansion over time. Radiation exposure increased lung macrophages, arterial wall thickness, fibroblast proliferation, and collagen deposition in peripheral and perivascular regions (p<0.001). Moreover, both STAT-3 and TGF-β positive cells were increased in lung parenchyma. Pulmonary hypertension developed, detected by echocardiography and confirmed by invasive RVSP measurement. RLR group exhibited increased kidney collagen deposition and tubular cell thickening (p=0.002). These findings demonstrate the systemic impact of radiation on cardiorespiratory function and kidney integrity.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting hyper-resistance to muscle stretch in cerebral palsy: muscle hypo-extensibility is more of an issue than hyperreflexia.","authors":"Pedro Valadão, Jean-Michel Gracies, Francesco Cenni, Lynn Bar-On, Harri Piitulainen, Janne M Avela, Taija Finni","doi":"10.1152/japplphysiol.00965.2024","DOIUrl":"https://doi.org/10.1152/japplphysiol.00965.2024","url":null,"abstract":"<p><p>Hyper-resistance to passive muscle stretch is a common debilitating symptom of spastic paresis. Although straightforward to assess, hyper-resistance is caused by a complex interaction of altered tissue properties, stretch hyperreflexia and involuntary background muscle activation. Identifying the contribution of each underlying component causing hyper-resistance is of great significance for designing treatments. The aim of this study was to investigate the components contributing to ankle plantarflexors' hyper-resistance in spastic cerebral palsy. We compared ankle biomechanical and reflex variables during ankle plantarflexors stretches at various velocities in fifteen individuals with mild spastic cerebral palsy (GMFCS I, age range: 9-22 years, 10 males) vs. fifteen age- and sex-matched typically developing controls. In addition, we evaluated associations between biomechanical and reflex variables. The cerebral palsy group had a median 9° lower maximum passive dorsiflexion range of motion at slow stretch velocity (p = 0.001), a 9° lower stretch reflex threshold (p < 0.01) with higher stretch reflex response magnitude (p ≤ 0.001) for both soleus and medial gastrocnemius muscles, and higher peak torques at fast stretch velocities (p < 0.01). When normalized to the maximum passive range of motion, stretch reflex thresholds were not different between groups. While hyperreflexia directly contributed to hyper-resistance, normalized stretch reflexes did not occur earlier in the stretch in individuals with cerebral palsy compared to typically developing controls, suggesting a direct influence of muscle hypo-extensibility on hyperreflexia. Treatments for hypo-extensibility are urgently needed, more so than treatments to reduce hyperreflexia.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concerns Regarding the Standard Deviation of Individual Responses for Assessing Treatment Response Heterogeneity.","authors":"Aaron R Caldwell, David B Allison, Andrew W Brown, Gary L Gadbury, Thirupathi Reddy Mokalla, R Drew Sayer, Andrew D Vigotsky","doi":"10.1152/japplphysiol.00485.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00485.2025","url":null,"abstract":"<p><p>The estimation of treatment response heterogeneity (TRH) is increasingly important as medicine moves toward personalized approaches. While various statistical methods have been proposed to quantify TRH in parallel-group trials, the standard deviation of individual responses (SD_IR) has gained prominence within physiological research. This method is intended to quantify individual response variation by comparing standard deviations of change scores between intervention and control groups. We acknowledge that SD_IR represents an improvement over many other flawed approaches that often involve responder counting. However, SD_IR has critical limitations: 1) it cannot overcome the fundamental problem of causal inference because the correlation between potential outcomes remains unidentifiable, 2) it is incorrectly predicated on the assumption that TRH is present only when treatment group variance exceeds control group variance, and 3) it is statistically inefficient. We present an alternative framework, which involves assessing heteroskedasticity and estimating the bounds for the standard deviation of treatment effects (SD_D). The presence of heteroskedasticity between treatment groups is a sufficient but not necessary condition for the presence of TRH. Further, SD_D makes fewer assumptions than SD_IR and, therefore, paints a more complete picture of potential TRH. Using data from a published exercise physiology study, we demonstrate how SD_D can better characterize uncertainty in TRH estimation. We recommend researchers probe TRH by assessing heteroskedasticity, providing bounds for SD_D, and estimating outcome distributions and probabilities while carefully crafting the theoretical rationale for the presence of TRH.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific survival but not tissue wasting in the KPP mouse model of pancreatic cancer-induced cachexia.","authors":"Natalia M Weinzierl, Jayarani Putri, Kathryn M Spitler, Erin E Talbert","doi":"10.1152/japplphysiol.00706.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00706.2025","url":null,"abstract":"<p><p>Cancer cachexia, a multifactorial condition resulting in muscle and adipose tissue wasting, reduces the quality of life of many people with cancer. Cachexia is highly prevalent in people with pancreatic ductal adenocarcinoma (PDAC), and many animal models of pancreatic cancer are used to understand mechanisms underlying cachexia. One such model is the <i>Kras_LSL-G12D</i>, <i>Ptf1a^Cre-ER/+</i>, <i>Pten^flox/flox</i> (KPP) model, which utilizes an inducible Cre recombinase to initiate tumor development by tamoxifen administration. In our previous work, tumors were induced in KPP mice at 4 weeks of age. However, mice are rapidly growing at this age, and a portion of the body weight differences seen between control and KPP mice is likely due to slowed growth of KPP mice. In our current study, pancreatic tumors were induced to develop with tamoxifen in KPP mice after rapid postnatal growth has slowed at 10 weeks of age (KPP10). Given the expanding evidence of sexual dimorphisms in cancer cachexia, we utilized both male and female mice to assess potential sex differences. Similar to our previous findings, KPP10 mice had lower body, muscle, and adipose tissue weights compared to non-tumor mice, and these differences were similar between male and female mice. However, male mice experienced greater relative weight loss. Unexpectedly, we identified that survival was significantly shorter in female KPP10 mice compared to KPP10 males. Greater body weight at tumor induction was associated with longer survival, suggesting that the sex difference in survival may be related to differences in body weight between male and female mice.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in performance fatigability after a maximal intermittent fatiguing protocol with a flywheel device.","authors":"Jorge Salse-Batán, Michel Marina, Priscila Torrado","doi":"10.1152/japplphysiol.00307.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00307.2025","url":null,"abstract":"<p><p>This study aimed to determine whether sex influences neuromuscular modulation following a maximal intermittent fatiguing protocol (IFP_max) using a flywheel device (FD; moment of inertia: 0.13 kgꞏm²). A secondary objective was to assess the recovery of force and electromyographic signals. Thirty-six young adults (20 females) completed 10 sets of 10 half-squats with 3-min rest intervals. Knee extension force was assessed during maximal voluntary isometric contraction (MVC) at pre-fatigue (PRE), following the IFP_max (POST), and after a recovery of 10-min (P10). Additionally, femoral nerve stimulation, such as doublets at 100 Hz (Db₁₀₀) and 10 Hz (Db₁₀) and single twitches (Tw) were applied to obtain electrically-evoked mechanical and electromyographic responses, voluntary activation (VA), H-reflex, and superimposed and resting M-wave variables at the three time points. Although males demonstrated higher pre-fatigue MVC values, they experienced a larger decline at POST (-42% vs -31%; P = 0.032). Electrically-evoked forces remained reduced at P10 compared to PRE (P < 0.001). Males showed greater declines in peak Tw (-63% vs -51%; P = 0.049), Db₁₀ (-70% vs -58%; P = 0.021) and Db_10:100 ratio (-39% vs -30%; P = 0.041). Overall, M-wave variables showed similar decrements in both sexes. Irrespective of sex, VA and H-reflex decreased at POST (P ≤ 0.037). The IFP_max performed using a FD induced a pronounced peripheral fatigue, with contractile mechanisms being more impaired in males. In contrast, central adjustments were similar between sexes. Future research is warranted to determine the most effective strength training strategies tailored to sex-specific responses.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific protective effects of angiotensin II type 1 receptor knockdown on disuse muscle atrophy in the rat soleus muscle.","authors":"Toshinori Yoshihara, Mizuki Takaragawa, Shohei Dobashi, Hisashi Naito","doi":"10.1152/japplphysiol.00731.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00731.2025","url":null,"abstract":"<p><p>Skeletal muscle disuse leads to atrophy. Accumulating evidence suggests that angiotensin II type 1 receptor (AT1R) contributes to sex-dependent catabolic signaling. However, the direct role of AT1R in skeletal muscle is unclear. This study investigated whether selective suppression of AT1R expression in the rat soleus muscle via adeno-associated virus serotype 9 (AAV9)-mediated short hairpin RNA (shRNA) delivery could mitigate hindlimb unloading (HU)-induced muscle atrophy, and whether this effect differed between male and female rats. Male and female rats received intramuscular injections of AAV9 vectors encoding AT1R-targeted shRNA into the soleus muscle. After 7 d of HU, <i>AT1R</i> gene copy number (digital PCR), receptor abundance (ligand binding assay), muscle fiber cross-sectional area (CSA), and downstream molecular markers (including phosphorylated Smad2/3 and Smad1/5/8, HDAC4 expression, and the atrogenes, <i>Fbxo32</i> and <i>Trim63</i>) were assessed. Female rats exhibited substantially higher <i>AT1R</i> gene copy numbers, which were selectively reduced by AAV9-shRNA. Ligand binding confirmed reduced receptor abundance in both sexes. CSA loss attenuation was observed exclusively in females, particularly in type I fibers. In female animals, AT1R knockdown substantially increased Smad1/5/8 phosphorylation and decreased HDAC4 expression. The AT1R copy number was positively correlated with <i>Fbxo32</i> and <i>Trim63</i> expression, independent of AAV dose. AT1R plays a sex-specific role in disuse-induced muscle atrophy, as muscle-specific AT1R knockdown conferred selective protection in female rats. The effect appears to be mediated via Smad1/5/8-HDAC4 signaling rather than oxidative stress or autophagy. This study provides mechanistic support for sex-informed therapeutic strategies targeting the muscle-localized renin-angiotensin system.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}