Journal of applied physiology最新文献

{"title":"Effects of aging on the vasoconstrictor reactivity and potassium channel regulation of diaphragm arterioles from male and female Fischer-344 rats.","authors":"Andrew G Horn, Kristina H Morrison, Kiana M Schulze, Sarah A Fenn, Judy Muller-Delp, David C Poole, Bradley J Behnke","doi":"10.1152/japplphysiol.00152.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00152.2025","url":null,"abstract":"<p><p><b>INTRO:</b> Regional diaphragm hemodynamics are compromised with advanced age. Evidence suggests that age-related alterations in diaphragm blood flow distribution may be related to a decline in the vasoconstrictor reactivity of the diaphragm resistance vasculature. In medial costal diaphragm first order (1A) arterioles, we hypothesized that aging would be associated with blunted myogenic vasoconstriction and increased potassium (K⁺) channel modulation of myogenic tone. <b>METHODS:</b> In young (Y) and old (O) Fischer-344 rats (n=71), medial costal diaphragm 1A arterioles (112 - 220 µm) were isolated, cannulated, and pressurized via hydrostatic fluid reservoirs. Vasoconstrictor responses to increased intraluminal pressure (myogenic), potassium chloride (KCl)-induced) and passive pressure diameter responses were assessed. In a separate set of arterioles, myogenic responses were evaluated in the presence and absence of the BK_Ca channel blocker iberiotoxin (IBX; 30 nM) and IBX plus the K_V channel inhibitor 4-aminopyridine (4-AP; 5 mM). <b>RESULTS:</b> Myogenic constriction was blunted (<i>P = 0.038</i>) and K⁺-induced constriction was decreased in medial costal 1A arterioles from O versus Y rats (44 ± 8% vs. 58 ± 7%; P < 0.001). BK_Ca channel inhibition increased myogenic constriction to the same extent in medial costal 1A arterioles from Y and O rats whereas combined BK_Ca and K_V channel blockade abolished the age-related differences in myogenic constriction. <b>CONCLUSION:</b> In medial costal diaphragm arterioles, aging is associated with: 1) impaired myogenic and K⁺-induced vasoconstriction, and 2) increased K_V channel modulation of myogenic tone. These alterations in vasoconstrictor function provide novel vascular mechanisms contributing to age-related diaphragm blood flow dysregulation.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144496778","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":"Chemistry vs. compensation: Comparing integrated respiratory-renal responses between acute inspired normobaric hypoxia vs. sustained hypobaric hypoxia.","authors":"Nicole A Johnson, Nicholas Strzalkowski, Monica K Russell, Christian A Clermont, Jennifer M Demarty, Leo C Transfiguracion, John F Horton, Michael J Asmussen, Trevor A Day","doi":"10.1152/japplphysiol.01014.2024","DOIUrl":"https://doi.org/10.1152/japplphysiol.01014.2024","url":null,"abstract":"<p><p>During acute exposure to hypoxia, peripheral respiratory chemoreceptors detect decreases in blood oxygenation, eliciting a hypoxic ventilatory response (HVR), which is enhanced with the duration and intensity of exposure (ventilatory acclimatization). The HVR protects oxygenation, but a secondary consequence is the elimination of PaCO₂, resulting acutely in hypocapnia and respiratory alkalosis. With sustained exposure to hypobaric hypoxic conditions (e.g., high altitude ascent; HA), the renal tubules reduce HCO₃- reabsorption and H+ excretion, excreting HCO₃ - and retaining H⁺, returning arterial pHa toward normal values. We aimed to characterize and compare blood oxygenation and acid-base homeostasis between two models of hypoxic exposure with matching P_IO₂ (~74-76 mmHg): acute hypoxic exposure eliciting an HVR-mediated hypocapnia over 24-min vs. sustained hypoxic-hypocapnia with incremental ascent to HA over 10-days. Using arterial blood draws, we measured PaO₂, SaO₂, PaCO₂, [HCO₃ ^-]a and pHa, obtained before and following (a) acute stepwise reductions in FIO2 for ~24-min, with the last step being an F_IO₂ of 0.12 (P_IO₂≅74mmHg) and (b) sustained exposure to hypoxia during incremental ascent to 5,200m over 10-days (P_IO₂≅76mmHg). We found that (a) acute normobaric hypoxia elicited hypocapnia and respiratory alkalosis, as expected, and (b) after sustained exposure to hypobaric hypoxia, there was persistent alkalosis, despite appreciable renal compensation. These findings highlight the time-course and magnitude of integrated respiratory responses and subsequent renal compensation mounted by the kidneys, specifically that the hypoxia-mediated hypocapnia and respiratory alkalosis experienced at 5,200m is likely beyond the threshold for a full renal compensation in healthy lowlanders.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317002","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 lipidome and proteome of high-density lipoprotein are altered in menopause.","authors":"Satu Lehti, Tia-Marje Korhonen, Rabah Soliymani, Hanna Ruhanen, Emilia Lähteenmäki, Mari Palviainen, Pia Siljander, Maciej Lalowski, Reijo Käkelä, Maarit Lehti, Eija K Laakkonen","doi":"10.1152/japplphysiol.00120.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00120.2025","url":null,"abstract":"<p><p>High-density lipoprotein particles (HDL) possess anti-inflammatory, anti-thrombotic, cytoprotective, and anti-oxidative properties, thus protecting against cardiovascular diseases. Menopause is associated with changes in serum metabolome and HDL size distribution. We analyzed the protein and lipid composition of the HDL particles from pre-, peri-, and postmenopausal women (N=216) with nuclear magnetic resonance and mass spectrometry to get a deeper insight into the composition of HDL in different stages of menopause. Both particle size and composition differed; in perimenopause, the proportion of small HDL particles (8.7 nm on average) was higher, and the proportion of large HDL particles (12.1 nm on average) was lower than in pre- or postmenopause. In perimenopause, each particle size class was enriched with triacylglycerols, and the calculated lipid class ratio of triacylglycerol/cholesteryl ester was the highest within perimenopausal HDL particles. This potentially affects HDL interaction with lipid-modifying enzymes. We also observed directionally opposite associations for HDL cholesteryl ester and unesterified cholesterol with systemic estradiol and follicle-stimulating hormone levels, especially regarding S-sized HDL particles, but not the hormone associations with HDL triacylglycerols. Perimenopausal HDL exhibited a lower proportion of apolipoproteins (apoA-I, apoA-II, apoC-I, apoC-III, apoD and apoE) per particle than premenopausal or postmenopausal HDL. In summary, we found that premenopausal and postmenopausal HDL particles were compositionally similar and differed from perimenopausal ones. We suggest that menopause, and especially the unbalanced hormonal state in perimenopause, are reflected in the lipid and protein compositions of the HDL, which, in turn, may affect the functions of the HDL particle during menopause.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225527","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":"Seven (.65) seconds away: the possibility and physiology of a women's sub-4 min mile.","authors":"Rebekah J Osborne, Brett S Kirby, Matthew I Black, Anni Vanhatalo, Andrew M Jones","doi":"10.1152/japplphysiol.00074.2025","DOIUrl":"10.1152/japplphysiol.00074.2025","url":null,"abstract":"","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1335-1340"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063948","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":"Twenty-one days of bed rest alter motor unit properties and neuromuscular junction transmission in young adults.","authors":"Fabio Sarto, Miloš Kalc, Evgeniia S Motanova, Martino V Franchi, Daniel Stashuk, Nina Murks, Giacomo Valli, Samuele Negro, Tomaž Prašnikar, Mladen Gasparini, Giovanni Martino, Giuseppe De Vito, Aleš Holobar, Boštjan Simunič, Rado Pišot, Marco V Narici","doi":"10.1152/japplphysiol.00178.2025","DOIUrl":"10.1152/japplphysiol.00178.2025","url":null,"abstract":"<p><p>Previous studies showed that properties of higher-threshold motor units (MUs) and neuromuscular junction (NMJ) function are preserved during short-term disuse. This study aimed to test how a longer disuse period affects MU properties, NMJ transmission, and NMJ morphology remodeling. Nine young healthy males (age: 18-29 yr) underwent 21 days of horizontal bed rest. Pre- (BR0) and postbed rest (BR21), quadriceps maximal voluntary contraction (MVC), and size were assessed. We combined intramuscular electromyography (iEMG) and high-density surface electromyography (HDsEMG) recordings on the vastus lateralis to assess MU properties at 25% and 50% of MVC. Muscle biopsies and blood samples were also collected. Quadriceps MVC and size decreased at BR21. We found alterations in MU properties at both contraction intensities, including reduced discharge rate, MU potential area changes, and increased complexity. NMJ transmission was found to be reduced at BR21 at 25% MVC. This functional NMJ impairment was biochemically corroborated by an increase in serum C-terminal agrin fragment concentration, a biomarker of NMJ instability. In addition, a direct assessment of NMJ morphology revealed the presence of some denervated NMJs exclusively at BR21. In conclusion, 21-day bed rest altered MU properties across different contraction intensities and impaired NMJ transmission with initial signs of remodeling/denervation. Disuse duration appears to be a critical factor, as previous shorter studies failed to detect some of these changes. We believe these findings are clinically relevant for disuse after trauma, surgery, or illness and may support the development of effective countermeasures.<b>NEW & NOTEWORTHY</b> Leveraging both intramuscular and high-density surface EMG recordings in the vastus lateralis, we identified alterations in motor unit (MU) properties in young adults after 21 days of bed rest. These included reduced discharge rates and changes in MU potential size and complexity, observed at both low and moderate contraction intensities. Evidence of impaired neuromuscular junction (NMJ) function and denervation was also found. Our findings indicate that medium-term disuse elicits MU-level changes not detected in shorter-duration studies.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1411-1424"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019625","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":"Global mitophagy inhibition via BNIP3 ablation is not sufficient to alleviate skeletal muscle impairments in male and female tumor-bearing mice.","authors":"Francielly Morena, Ana Regina Cabrera, Toby L Chambers, Pieter J Koopmans, Seongkyun Lim, Stavroula Tsitkanou, Sabin Khadgi, Calvin Peterson, Eleanor R Schrems, Ruqaiza Muhyudin, Sepideh Shakeri, Kevin Zhao, Devan Mishra, Tyrone Washington, Kevin A Murach, Nicholas P Greene","doi":"10.1152/japplphysiol.00009.2025","DOIUrl":"10.1152/japplphysiol.00009.2025","url":null,"abstract":"<p><p>Cancer cachexia (CC) is marked by severe skeletal muscle loss and dysfunction, associated with mitochondrial degeneration. Our previous studies showed induction of the mitophagy marker BNIP3 3-wk post-Lewis lung carcinoma (LLC) induction. We hypothesize that excessive mitophagy contributes to muscle wasting in CC. To test this, we used a <i>Bnip3</i> knockout (KO) mouse model with LLC-induced CC to assess its impact on muscle outcomes. Eight-wk-old male and female mice were injected with 1 × 10⁶ LLC cells or PBS (sham controls). After 4 wk, we assessed muscle function through dorsiflexor electrophysiology, muscle protein synthesis via deuterium oxide labeling, and mitochondrial respiration. Plantaris and white gastrocnemius muscles were analyzed for mitochondrial respiratory function, tibialis anterior (TA) for muscle cross-sectional area, and mixed gastrocnemius for protein and mRNA analysis. <i>Bnip3</i> KO showed some benefits in males, including attenuated fat loss and splenomegaly and near-significant attenuation of extensor digitorum longus (EDL) mass loss. In females, <i>Bnip3</i> KO did not prevent relative muscle atrophy or functional impairments. In males, KO lowered protein synthesis independent of cancer. Despite KO reducing mitophagy markers, it did not improve muscle mitochondrial respiration or functional outcomes. In both sexes, KO mice exhibited unbalanced mitochondrial dynamics with increased fission and reduced fusion, processes also impaired by LLC. Overall, global <i>Bnip3</i> ablation may not offer significant benefits for CC by itself. These findings suggest that targeting aberrant mitophagy via complete <i>Bnip3</i> deletion is insufficient to alleviate cancer-induced muscle detriments in both biological sexes, whereas BNIP3-mediated mitophagy may be needed to maintain protein anabolism.<b>NEW & NOTEWORTHY</b> Global Bnip3 KO alleviates loss of fat mass and splenomegaly in LLC-bearing male and female mice. Bnip3 deletion is insufficient to attenuate relative muscle loss. BNIP3 appears essential for normal muscle protein anabolism and contractile function in males but not females, regardless of the tumor-bearing state.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1516-1531"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cumulative effects of training at different weekly energy expenditures on cardiorespiratory fitness and markers of metabolic syndrome in STRRIDE-Extension.","authors":"Garrett A Moseley, Leanna M Ross, Katherine A Collins-Bennett, Rebecca North, Johanna L Johnson, William E Kraus","doi":"10.1152/japplphysiol.00743.2024","DOIUrl":"10.1152/japplphysiol.00743.2024","url":null,"abstract":"<p><p>Assess the cumulative effects of different weekly exercise energy expenditures, with similar total program volume and intensity, on cardiorespiratory fitness (CRF) and metabolic syndrome (MetS). Following the 9-mo Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) trial, 22 participants continued exercise training for 6-24 mo in one of two groups: <i>1</i>) low-amount/vigorous-intensity (LAVI; <i>n</i> = 14): 14 kcal/kg/wk (KKW) at 65%-80% peak V̇o₂ and <i>2</i>) high-amount/vigorous-intensity (HAVI; <i>n</i> = 8): 23 KKW at 65%-80% peak V̇o₂. Outcomes included absolute (AV̇o₂) and relative peak oxygen consumption (RV̇o₂), body fat percentage, waist circumference, HDL-C, triglycerides, fasting glucose, insulin sensitivity index (S_I), and modified MetS <i>z</i> score. Group comparisons were made at equivalent and differential timepoints with similar total exercise volumes. S_I improvements were greater in HAVI compared with LAVI at the LAVI 21-mo/HAVI 15-mo contrast (mean difference ± SD: 2.13 ± 0.68 mU/L/min, <i>P</i> = 0.008). AV̇o₂ and RV̇o₂ improvements were greater in HAVI at both the LAVI 21-mo/HAVI 15-mo contrast (model estimate [95% CI]: 0.21 [0.01, 0.40] L/min, <i>P</i> = 0.038 and 3.05 [0.14, 5.96] mL/kg/min, <i>P</i> = 0.041), respectively, and the LAVI 33-mo/HAVI 21-mo contrast (0.25 [0.04, 0.45] L/min, <i>P</i> = 0.022 and 3.21 [0.10, 6.32] mL/kg/min, <i>P</i> = 0.044). These AV̇o₂ contrasts remained significant after adjusting for age and sex. Adherence declined over time. When cumulative exercise volumes were similar, body composition and MetS markers adapted similarly between groups. However, continued training at greater weekly volumes of vigorous exercise resulted in more substantial CRF and S_I improvements compared with lesser weekly volumes. Findings suggest factors beyond total energy expenditure-such as exercise frequency or duration-may modulate some longitudinal health improvements.<b>NEW & NOTEWORTHY</b> This exploratory analysis investigated longitudinal effects of accumulating similar total exercise program volumes at different weekly exercise energy expenditures on cardiorespiratory fitness and metabolic syndrome measures over months to years. In general, adaptations are similar; however, factors other than total energy cost-such as exercise frequency or duration-may modulate longitudinal improvements in cardiorespiratory fitness and skeletal muscle insulin sensitivity over 33 mo of training among sedentary adults with overweight or obesity and dyslipidemia.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1532-1542"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sexual dimorphism in animal models of heart failure with preserved ejection fraction.","authors":"Maria Bauer, Mahin Gadkari, Marta Martinez Yus, Lakshmi Santhanam, Jochen Steppan","doi":"10.1152/japplphysiol.00595.2024","DOIUrl":"10.1152/japplphysiol.00595.2024","url":null,"abstract":"<p><p>Heart failure is a complex clinical syndrome that continues to be a leading cause of cardiovascular morbidity and mortality around the world. Despite major advances in its treatment and management, the rate of hospitalization and mortality has remained unchanged in the past decade. Heart failure with preserved ejection fraction (HFpEF) accounts for more than half of all incident-based hospital admissions for decompensated heart failure and represents a global healthcare problem. Moreover, its incidence rate among all heart failures is increasing, and survival rates are significantly <50% at 5 years. Importantly, HFpEF disproportionately affects women after menopause, with female sex being independently associated with the prevalence of HFpEF and worse outcomes. The pathophysiology and critical molecular mechanisms underlying the progression of the abnormalities of this multifaceted syndrome are incompletely understood, and no evidence-based and target-directed treatment is available to prevent or cure its structural and functional myocardial dysfunction. To overcome this knowledge gap and develop targeted HFpEF therapies, animal models remain at the forefront of cutting-edge research studies. However, this is complicated by the lack of suitable animal models available that recapitulate the HFpEF phenotype in both sexes. This narrative review provides an overview of clinical features of the disease in both sexes and details carefully selected animal models with a particular focus on their ability to replicate sex-based differences.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1449-1473"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12158627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Motor unit discharge and torque steadiness are reduced in people with multiple sclerosis when performing voluntary muscle contractions.","authors":"Marc C Bruneau, Benjamin I Goodlich, Tyler T Henderson, Sean A Horan, Justin J Kavanagh","doi":"10.1152/japplphysiol.00096.2025","DOIUrl":"10.1152/japplphysiol.00096.2025","url":null,"abstract":"<p><p>Although people with multiple sclerosis (MS) often report symptoms of muscle weakness and motor fatigue, it is largely unknown how motor unit discharge and force generation are affected by the disease. The current study recruited 13 individuals with relapsing remitting MS (age range: 33-56 yr) and age-, sex-, and height-matched controls to perform submaximal isometric knee extensions at 30%, 50%, and 70% of maximal voluntary contraction (MVC). Motor unit discharge properties were extracted from high-density electromyography (HD-EMG) of the vastus lateralis, and the coefficient of variation of torque was used to assess torque steadiness. All data were collected before and after a motor fatigue task, which consisted of sustained MVCs that reduced knee extension torque to 60% of baseline MVC. Compared with healthy controls, the MS group had reduced maximal knee extension torque (-23%, <i>P</i> = 0.042), reduced discharge rate (-0.88 pps, <i>P</i> = 0.003), and increased torque coefficient of variation (CV) (+0.014, <i>P</i> = 0.006) during submaximal baseline contractions. The MS group had a shorter time-to-task failure for sustained MVCs (-19.3 s, <i>P</i> < 0.001), reduced discharge rate (-0.95 pps, <i>P</i> = 0.002), and increased torque CV (+0.039, <i>P</i> < 0.001) compared with controls following the sustained MVCs. Rating of perceived exertion was higher in the MS group compared with controls after the performance of the sustained MVCs (+18%, <i>P</i> < 0.001). These findings indicate that reduced motor unit discharge and torque steadiness are a feature of MS regardless of whether submaximal contractions are performed in the presence of motor fatigue.<b>NEW & NOTEWORTHY</b> Multiple sclerosis (MS) is characterized by inflammation and scarring in the nervous system that can cause severe motor dysfunction. This study reveals that discharge rate and torque steadiness are reduced in MS compared with age- and sex-matched healthy controls, which is consistent for regular submaximal contractions and submaximal contractions that are performed in the presence of motor fatigue. The findings highlight consistent impairments in muscle activation that contribute to MS motor dysfunction.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1505-1515"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149387","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 role of β-adrenergic receptors in mediating exercise hyperemia during incremental single-leg knee extension in young males and females.","authors":"Connor J Doherty, Benjamin P Thompson, Paige J Rynne, Jou-Chung Chang, Alexis E Pulford-Thorpe, Sarah A Angus, Eva C M Fleming, Sean L Gartner, Jason S Au, Glen E Foster, Paolo B Dominelli","doi":"10.1152/japplphysiol.00896.2024","DOIUrl":"10.1152/japplphysiol.00896.2024","url":null,"abstract":"<p><p>Previous research has identified a role for β-adrenergic receptors in mediating sex differences in blood pressure regulation at rest. β-receptors are also involved in the exercise hyperemia response during low-intensity small muscle mass exercise in males. However, less is known about β-adrenergic receptors in mediating local exercise hyperemia response during graded large muscle mass exercise in young males and females. We compared steady-state cardiorespiratory responses, leg blood flow (Q̇_LEG), and leg vascular conductance (LVC) in 16 participants (8 females) at rest and during incremental knee extension exercise with and without complete nonselective β-adrenergic blockade using propranolol. Propranolol reduced absolute heart rate (HR), Q̇_LEG, and LVC responses during exercise. Females had greater absolute increases in HR and lower absolute Q̇_LEG and LVC during exercise. However, Q̇_LEG and LVC responses to incremental exercise were not different by sex or propranolol, even after normalizing for differences in estimated quadriceps muscle mass. Females were also found to have greater dilation of the femoral artery, which was blunted to a greater extent with propranolol compared with males at absolute exercise intensities. In conclusion, β-adrenergic receptors did not play an important role in mediating the overall exercise hyperemia response in males or females, as the cardiovascular system prioritizes the preservation of oxygen delivery to the exercising muscle. However, β₂-adrenergic receptors appear to play a distinct role in mediating sex differences in changes to vascular tone during exercise.<b>NEW & NOTEWORTHY</b> We examined the role of beta-adrenergic receptors (β-ARs) in mediating exercise hyperemia in males and females. No sex differences in leg blood flow or leg vascular conductance, but females exhibited greater dilation of the femoral artery (FA), and β-AR blockade blunted FA dilation in females at absolute exercise intensities. Findings highlight that exercise hyperemia is not reliant on β-ARs and suggest females rely more on β-ARs in mediating vascular tone during exercise.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1664-1679"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025497","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}