American journal of physiology. Regulatory, integrative and comparative physiology最新文献

{"title":"BCAAs, LAT1, and the metabolic competition between tumor and peripheral tissues during cancer cachexia.","authors":"Jessica L Halle, Benjamin F Miller","doi":"10.1152/ajpregu.00219.2026","DOIUrl":"10.1152/ajpregu.00219.2026","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R229-R231"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410031","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":"Gravitational load, sex, and age-sex effects on cardiovascular compensatory responses during sit-to-stand and lie-to-stand transitions.","authors":"Dihogo Gama de Matos, Jefferson Lima de Santana, Felipe J Aidar, Stephen M Cornish, Gordon G Giesbrecht, Albena Nunes-Silva, Satish R Raj, Roman Romero-Ortuno, Todd A Duhamel, Rodrigo Villar","doi":"10.1152/ajpregu.00019.2026","DOIUrl":"10.1152/ajpregu.00019.2026","url":null,"abstract":"<p><p>Active postural transitions impose rapid orthostatic stress that requires coordinated cardiovascular compensation. Whether the magnitude and timing of these responses differ by gravitational load, age, and sex during common daily movements remains unclear. This study compared short-term cardiovascular regulation during sit-to-stand (lower gravitational load) and lie-to-stand (higher gravitational load) transitions in younger and older adults. Fifty-six healthy participants (younger and older females and males; <i>n</i> = 14/group) completed both transitions in a randomized, counterbalanced design. Beat-to-beat blood pressure and hemodynamic responses were assessed at baseline, immediately on standing, and across four predefined compensatory phases. General linear models examined the effects of condition, age, sex, and age-sex interactions, with cardiovascular medication included as a covariate. Lie-to-stand elicited larger immediate reductions in systolic, diastolic, and mean arterial pressure, alongside greater heart rate increases, compared with sit-to-stand (all <i>P</i> < 0.001). Older adults demonstrated larger drops in blood pressure and systemic vascular resistance, and blunted heart rate and cardiac output responses, particularly under higher gravitational load. In contrast, older adults maintained relatively higher stroke volume during lie-to-stand, suggesting greater reliance on mechanical compensation. Sex-related differences were condition-specific: younger males exhibited higher cardiac output during sit-to-stand, whereas older females showed higher late-phase mean arterial pressure and vascular resistance during lie-to-stand. These findings indicate that gravitational load strongly influences short-term cardiovascular compensation during active standing and amplifies age-related differences. Sit-to-stand and lie-to-stand transitions provide complementary information, highlighting the importance of considering transition type when evaluating orthostatic cardiovascular regulation.<b>NEW & NOTEWORTHY</b> We show that the type of active standing maneuver alters short-term cardiovascular regulation. Rising from supine (lie-to-stand) produces larger blood pressure drops and amplifies age-related impairments in cardiovascular compensatory responses compared with sit-to-stand. Older adults rely more on stroke volume and show blunted heart rate and vascular adjustments, especially under higher gravitational load. Sex effects were modest and condition-specific, highlighting the stronger influence of age and gravitational stress on orthostatic cardiovascular control.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R173-R185"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337401","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":"Acute exercise reduces intranasal insulin-mediated elevations in blood pressure in aging adults with cardiometabolic risk.","authors":"Steven K Malin, David H Zald, Daniel J Battillo","doi":"10.1152/ajpregu.00119.2026","DOIUrl":"10.1152/ajpregu.00119.2026","url":null,"abstract":"<p><p>Insulin contributes to blood pressure (BP) regulation through, in part, effects on the brain. Whether exercise impacts brain insulin action in parallel with alterations in BP is unclear. The purpose of this study is to examine whether an acute exercise lowers BP after intranasal insulin (INI) and increases cerebral blood flow (CBF) in aging adults with cardiometabolic risk. In a counterbalanced design, 15 cognitively unimpaired (MoCA: 28.2 ± 1.3 au) adults [56.7 ± 2.1 yr; (maximal oxygen consumption) V̇o_2max: 23.9 ± 0.9 mL/kg/min] with obesity (BMI 31.8 ± 1.3 kg·m^-2) were randomized to a rest or acute treadmill exercise bout (70% V̇o_2max for 60 min) in the evening. The next morning, participants arrived fasted, and BP, heart rate, glucose, and insulin were assessed. Brainstem and hypothalamus CBF were then tested via pseudo-continuous arterial spin labeling (pCASL) MRI. INI (40 IU) was administered, and 30 as well as 90 min later, BP, heart rate, glucose, and insulin were measured. Then, a 75-g oral glucose tolerance test (OGTT) was provided, and outcomes were obtained every 30 min up to 120 min. Exercise had no effect on glucose following INI, although insulin was reduced during the OGTT (<i>P</i> < 0.05). Exercise blunted the rise in systolic BP after INI and during the entire protocol (both <i>P</i> < 0.05), independent of heart rate. Exercise raised CBF in the brainstem (<i>P</i> < 0.05) but not in the hypothalamus. However, the increase in fasting hypothalamus CBF correlated with reductions in INI-mediated systolic BP (<i>r</i> = -0.51, <i>P</i> = 0.05). In adults with cardiometabolic risk, an acute exercise bout blunted systolic BP rises after INI in parallel with increased fasting brainstem and hypothalamic CBF.<b>NEW & NOTEWORTHY</b> Insulin contributes to blood pressure regulation through, in part, effects on the brain. Here, an acute exercise bout blunted the rise in systolic blood pressure in response to intranasal insulin, independent of heart rate. Moreover, exercise increased brainstem cerebral blood flow (CBF) and increased hypothalamus CBF related to reduced systolic blood pressure after intranasal insulin. These findings suggest that exercise may impact brain insulin action as it relates to blood pressure in a clinically relevant population.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R147-R154"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248724","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":"Homeostatic adaptations of the amphibious fish <i>Polypterus</i> in terrestrial environments.","authors":"Yuki Kimura, Takaaki Ito, Norifumi Konno, Shinji Kanda, Susumu Hyodo, Masato Nikaido","doi":"10.1152/ajpregu.00338.2025","DOIUrl":"10.1152/ajpregu.00338.2025","url":null,"abstract":"<p><p>The water-to-land transition in early tetrapods during evolution would have required a compensatory mechanism for the body-fluid homeostatic function originally undertaken by the gills in the water. We compared physiological and renal transcriptomic responses of the amphibious bichir <i>Polypterus senegalus</i> reared in aquatic and experimental terrestrial conditions. Plasma Na⁺ concentration, osmolality, and ammonia did not differ significantly between treatments (water: 106.3 mM, 207.3 mosmol/kgH₂O, and 270.1 μg/dL; terrestrial: 103.0 mM, 201.5 mosmol/kgH₂O, and 308.9 μg/dL). By contrast, transcripts for epithelial sodium channel subunits and for ammonia transporters (Rh proteins) were significantly upregulated in kidneys under terrestrial conditions. These results indicate that <i>Polypterus</i> maintains plasma homeostasis on land and that renal transcriptional plasticity, particularly increased expression of sodium and ammonia transporters, may partially compensate for diminished branchial function. These findings suggest that renal plasticity in basal actinopterygians could have facilitated early vertebrate water-to-land transitions.<b>NEW & NOTEWORTHY</b> This study demonstrates that the amphibious fish <i>Polypterus</i> maintains plasma ion, osmolality, and ammonia homeostasis during terrestrial exposure by shifting key regulatory functions from the gills to the kidney. Renal expression and distal tubular localization of the epithelial sodium channel, reported here for the first time in a ray-finned fish, highlight a conserved renal strategy supporting life on land.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R215-R228"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350337","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":"Prolonged heat stress induces autophagy in mouse skeletal muscle.","authors":"Sau Qwan Yap, Melissa Roths, Swathy Krishna, Tori E Rudolph, Joshua T Selsby","doi":"10.1152/ajpregu.00190.2025","DOIUrl":"10.1152/ajpregu.00190.2025","url":null,"abstract":"<p><p>Environment-induced heat stress (HS) is a significant and expanding threat to human health and efficient agricultural production. In this investigation, we aimed to determine the extent to which HS impacted skeletal muscle health. We hypothesized that HS would decrease autophagosome degradation and autophagic flux in mouse skeletal muscle. To test this hypothesis, female C57 mice were exposed to thermoneutral (TN; 30°C) or heat stress (HS; 37.5°C) conditions for 24 h, and the gastrocnemius, soleus, and diaphragm muscles were immediately collected. A subset of mice was treated with colchicine to assess autophagic flux. Environment-induced HS increased rectal and subcutaneous temperatures by ∼2.0°C and decreased feed intake by 75% and body mass by 14%, without a change in muscle mass. In all muscles, 24 h of HS increased phosphorylated heat shock proteins (HSP) 27 by 1.47-fold to 4.5-fold compared with TN; however, HSPs 27, 60, 72, and 90 were similar between groups. We discovered HS increased autophagic flux in the gastrocnemius and diaphragm, but not soleus, without changes in most key autophagy regulatory proteins. Markers of mitophagy, regulators of mitochondrial architecture, and mitochondrial abundance were largely similar between groups for all muscles. Environment-induced HS increased endoplasmic reticulum (ER) stress regulators, binding immunoglobulin protein by 1.7-fold to 2.9-fold and phosphorylated (p)-inositol-requiring enzyme 1 by 1.84-fold to 2.75-fold in all muscles, and p-eukaryotic initiation factor 2 was increased 3.6-fold in soleus. Counter to our hypothesis, these data demonstrate that 24 h of HS did not decrease autophagosome degradation or flux across a range of muscles in a mouse HS model.<b>NEW & NOTEWORTHY</b> Subheat stroke thermic injury is currently a human and animal health threat that is predicted to rise by environmental forecasting models. The extent to which persistent environment-induced hyperthermia impacts skeletal muscle health is largely unknown. Our findings challenge current knowledge regarding heat stress-induced dysfunction and suggest skeletal muscle mounts muscle-specific response to thermic injury.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R198-R214"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148256876","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":"Phase-dependent autonomic responses to electric fan use during a prolonged 8-h heat exposure in older adults.","authors":"Andres E Carrillo, Fergus K O'Connor, Meghan N Cuza-Berry, Christophe L Herry, Andrew J E Seely, James J McCormick, Glen P Kenny","doi":"10.1152/ajpregu.00096.2026","DOIUrl":"10.1152/ajpregu.00096.2026","url":null,"abstract":"<p><p>Electric fans are commonly recommended for older adults to reduce heat strain, yet their effects on cardiac autonomic regulation during heat exposure remain unclear. This study examined phase-dependent heart rate variability (HRV) responses to fan use during prolonged heat exposure in older adults. Sixteen participants (6 females; 65-85 yr) completed three 8-h heat exposures (36°C, 45% relative humidity) with fan-generated air speeds of 0, 2, or 4 m/s. Core (rectal) temperature and a 3-lead electrocardiogram were continuously acquired. Based on temporal core temperature responses, heat exposure was divided into Initial Ramp-Up Phase (0-4 h) and Plateau Phase (4-8 h). Core temperature increased from 37.1 (0.3)°C to 38.0 (0.3)°C (<i>P</i> < 0.001) during Ramp-Up and remained stable at 38.1 (0.3)°C (<i>P</i> ≥ 0.627) during Plateau Phase. During Ramp-Up, in all conditions, heart rate (HR) increased (<i>P</i> < 0.001), whereas vagally mediated HRV indices including root mean square of successive differences (RMSSD), high-frequency power, and cardiac vagal index (CVI) decreased (<i>P</i> ≤ 0.001). During Plateau Phase, HR was lower and RMSSD was higher in 2 m/s compared with 0 m/s condition (<i>P</i> ≤ 0.035), whereas RMSSD and CVI were higher in 2 m/s compared with 4 m/s condition (<i>P</i> ≤ 0.021). We show that HRV responses to prolonged heat exposure in older adults are phase-dependent. Progressive heat storage during Ramp-Up induces HRV responses reflective of vagal withdrawal, regardless of fan use, whereas low-level airflow (2 m/s) during Plateau Phase modestly attenuated reductions in HRV. These findings suggest that the physiological effectiveness of fan use during extreme indoor heat may depend on air flow intensity and temporal progression of heat strain in older adults.<b>NEW & NOTEWORTHY</b> This study demonstrates that cardiac autonomic responses to prolonged heat exposure in older adults are phase-dependent. During the first 4 h of heat exposure (Initial Ramp-Up Phase), regardless of fan use, heart rate variability (HRV) indices reflective of vagal activity declined. Subsequently, during the last 4 h (Plateau Phase), low air flow from an electric fan was associated with modest improvements in HRV when compared with no fan or air flow at higher speeds.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R155-R163"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148292966","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":"Water intake mediates cross-sectional associations between urinary kidney injury biomarkers and race in emerging adults.","authors":"Jake P Muma, Braxton A Linder, Nina L Stute, Sofia O Sanchez, Christin Domeier, Joseph C Watso, Matthew C Babcock, Roger S Zoh, Orlando M Gutiérrez, Zachary J Schlader, Thomas E Fuller Rowell, Austin T Robinson","doi":"10.1152/ajpregu.00097.2026","DOIUrl":"10.1152/ajpregu.00097.2026","url":null,"abstract":"<p><p>Experimental hypohydration increases acute kidney injury (AKI) biomarkers, indicating potential kidney stress. Black adults are more likely to be underhydrated than White adults, yet it is unclear whether habitual hydration is associated with AKI biomarkers or whether racial differences exist, particularly in emerging adults. Fifty-four participants (24 Black/30 White, 27 M/27 F, age: 21 ± 1 yr, mean ± SD) provided diet diaries to assess water intake and 24-h urine samples. We assessed hydration biomarkers [urine osmolality, urine specific gravity (USG)], creatinine clearance, and urinary AKI biomarkers, including kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), thioredoxin-1 (TRX-1), tissue inhibitor of metalloproteinase 2 (TIMP-2), insulin-like growth factor binding protein 7 (IGFBP7), and TIMP-2 × IGFBP7. Black adults exhibited higher USG (<i>P</i> = 0.043) and urine osmolality [534(506) vs. 303(541) mosmol/kgH₂O, <i>P</i> = 0.007, median (IQR)], and reported lower water intake (<i>P</i> < 0.001), but there was no difference in creatinine clearance (<i>P</i> = 0.250) compared with White adults. Black adults exhibited higher urinary NGAL, TIMP-2, IGFBP7, and TIMP-2 × IGFBP7 (ps ≤ 0.034) concentrations, but not urinary KIM-1 or TRX-1 (ps ≥ 0.096) concentrations. When indexed to urine flow rate, the racial difference persisted only for TIMP-2 × IGFBP7 [319(467) vs. 215(214) [ng/mL]²/min, <i>P</i> = 0.014]. In a regression model with sex, urine osmolality, and water intake (<i>R</i>² = 0.596, <i>P</i> < 0.001), race was no longer associated with TIMP-2 × IGFBP7 (<i>P</i> = 0.168). Mediation analysis revealed that water intake mediated 82.6% (<i>P</i> = 0.007) of the race difference in TIMP-2 × IGFBP7 (overall <i>P</i> = 0.015). Racial disparities in urinary TIMP-2 × IGFBP7 excretion between emerging Black and White adults may be mediated by water intake differences.<b>NEW & NOTEWORTHY</b> Apparently healthy emerging Black adults exhibited higher concentrations of several kidney injury biomarkers, collected via a 24-h urine sample, compared with White adults. Racial group differences in all kidney injury biomarkers tested, except for TIMP-2 × IGFBP7 (the only FDA-approved urinary kidney injury biomarker), were attenuated once indexed to urinary hydration markers. Water intake mediated the racial group difference in TIMP-2 × IGFBP7. Future work is needed to determine whether hydration interventions could mitigate racial differences in TIMP-2 × IGFBP7.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R113-R126"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148209829","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":"Early life stress blunts time-of-day-specific autonomic function in adult male mice.","authors":"Megan K Rhoads, David M Pollock, Keri M Kemp, Bryan K Becker, Jackson Colson, Jennifer S Pollock","doi":"10.1152/ajpregu.00023.2026","DOIUrl":"10.1152/ajpregu.00023.2026","url":null,"abstract":"<p><p>Early life stress (ELS) is an independent risk factor for cardiovascular disease, including hypertension. The current study was designed to test the hypothesis that exposure to ELS disrupts autonomic function in adult mice at baseline and in response to an acute behavioral stressor. Using the mouse model of ELS, maternal separation with early weaning (MSEW), we determined the effects of ELS on heart rate (HR), blood pressure (BP), locomotor activity (LMA), HR variability (HRV), and spontaneous baroreceptor sensitivity (sBRS) in adult male mice. Under basal conditions, normally reared (NR) and MSEW mice had similar HR, BP, LMA, and sBRS when characterized at different phases of the circadian cycle. Spectral analysis of HRV indicated that MSEW mice had significantly lower total power and low-frequency (LF) power during the inactive or light period, as well as a loss of diurnal rhythm of LF power compared with NR mice. When subjected to an acute behavioral stress, cage switch stress (CSS), NR and MSEW mice showed similar changes in HR, BP, and LMA. Frequency domain analysis of HRV indicated that total, LF, and high frequency power during CSS and recovery from CSS were all significantly decreased in MSEW mice compared with NR mice. Taken together, these findings indicate that exposure to ELS in mice disrupts autonomic function basally and in response to an acute behavioral stress in a time-of-day dependent manner.<b>NEW & NOTEWORTHY</b> Early life stress is a known risk factor for cardiovascular disease in adulthood. The current study provides evidence for impaired regulation of the autonomic nervous system in adult mice after being exposed to maternal separation with early weaning, an established model of neglect.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R164-R172"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148373748","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":"Emerging concepts in baroreflex regulation of action potential subpopulations in human muscle sympathetic nerve activity.","authors":"Stephen A Klassen","doi":"10.1152/ajpregu.00111.2026","DOIUrl":"10.1152/ajpregu.00111.2026","url":null,"abstract":"<p><p>Baroreflex regulation of muscle sympathetic nerve activity (MSNA) represents a key mechanism defending blood pressure homeostasis. The original human microneurographic studies generated convincing evidence that the baroreflex strongly shapes MSNA into bursts and influences variations in burst frequency but weakly regulates burst amplitude. This review synthesizes these foundational integrated MSNA observations with emerging multiunit action potential (AP) data to provide insight into baroreflex regulation of human sympathetic discharge during baseline and periods of physiological stress. The spontaneous baroreflex gain technique illustrates that differential baroreflex regulation of burst frequency versus amplitude stems from heterogeneous regulation over size-based AP subpopulations. During baseline, whereas medium APs that fire in most bursts exhibit strong baroreflex control, larger APs, which predominantly fire in large bursts, receive weak baro-regulation. During orthostasis, rises in MSNA are achieved by resetting the baroreflex operating point for medium APs upward to greater firing probabilities and positions of stronger baroreflex control. Also, we have documented a subpopulation of asynchronous APs that are synchronized into bursts during orthostasis. During fatiguing handgrip exercise, interactions between central feed-forward and metaboreflex mechanisms ensure that the strength of AP baroreflex control is maintained but reset upward to higher discharge and rightward to greater pressures. Also, during orthostasis and fatiguing exercise, total MSNA is augmented by recruiting larger previously silent APs under weak baroreflex control. These observations suggest the existence of subpopulations of sympathetic neurons that receive heterogeneous central baroreflex regulation. Transient AP baroreflex resetting may represent a strategy to support blood pressure homeostasis in humans.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R270-R282"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468397","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":"Hydrating with a higher-fructose sport drink does not worsen acute kidney injury risk during simulated work-related heat stress.","authors":"Erica Tourula, Molly E Heikkinen, Amanda Regester, Marley G Owen, Hayden W Hess, Lisa Spence, Timothy D Mickleborough, Blair D Johnson, Nana Gletsu-Miller, Zachary J Schlader","doi":"10.1152/ajpregu.00047.2026","DOIUrl":"10.1152/ajpregu.00047.2026","url":null,"abstract":"<p><p>Fructose-containing soft drinks worsen acute kidney injury (AKI) risk during simulated work-related heat stress (WrHS), but the fructose content is comparatively lower in sport drinks. This study tested the hypothesis that consuming a higher-fructose sport drink exacerbates AKI risk compared with consuming a sucrose-sweetened sport drink during a 4-h WrHS simulation. In this block randomized, double-blind crossover study, 12 healthy adults (26 ± 7 yr; 6 women) completed two trials involving ingesting six 500 mL doses of a higher-fructose sport drink (55% fructose and 45% glucose; Fructose55) or a sucrose-sweetened sport drink (50% fructose and 50% glucose; Sucrose) before, during, and following a 4-h WrHS simulation that comprised three circuits of treadmill walking (10 min) and rowing (5 min) at five metabolic equivalents and 15 min of rest every hour. Drinks were matched for total carbohydrates, calories, and electrolytes and modestly matched for osmolality. Urine and blood samples were collected pre- and postexposure, at recovery, and 24 h post-visit. AKI risk was quantified as the product of urine insulin-like growth factor-binding protein 7 and urine tissue inhibitor of metalloproteinase-2 ([IGFBP7·TIMP-2]) normalized to specific gravity. Peak rectal temperature (Fructose55: 38.3 ± 0.7°C, Sucrose: 38.3 ± 0.7°C, <i>P</i> = 0.991) and percent change in body weight (Fructose55: -0.7 ± 1.0%, Sucrose: -0.9 ± 1.0%, <i>P</i> = 0.466) were not different between trials. Urinary [IGFBP7·TIMP-2] increased over time (<i>P</i> < 0.001) but did not differ between trials (peak change-Fructose55: 1.7 ± 1.6 (ng/mL)²/1,000, Sucrose: 1.6 ± 1.8 (ng/mL)²/1,000, <i>P</i> = 0.677). Consuming a higher-fructose-containing sport drink does not exacerbate AKI risk during WrHS when compared with a sucrose-sweetened equivalent.<b>NEW & NOTEWORTHY</b> This study tested whether drinking a sport drink with a higher proportion of fructose influences acute kidney injury (AKI) risk during simulated work-related heat stress. In a block randomized, double-blind crossover design, healthy adults consumed either a higher-fructose or sucrose-sweetened sport drink matched for calories, electrolytes, and carbohydrates. Despite increases in AKI biomarkers with heat stress, the type of sugar in the sport drink did not alter AKI risk, indicating that modest differences in fructose content do not meaningfully impact kidney stress.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R127-R146"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262723","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}