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

{"title":"Warming up to a new coat: molting king penguins exhibit hyperthermia and increased peripheral heat loss.","authors":"Juan D Zuluaga, Emmanuel Pretti, Aude Leynaert, Elsa Marçon, Antoine Stier, Agnès Lewden","doi":"10.1152/ajpregu.00078.2025","DOIUrl":"10.1152/ajpregu.00078.2025","url":null,"abstract":"<p><p>Penguins are among the most specialized thermoregulators on the planet; however, the same adaptations that maximize heat retention underwater likely hinder heat dissipation on land, possibly creating dangerous thermoregulatory challenges when encountering warming terrestrial habitats. Penguins are subject to strictly terrestrial phases, such as molting, when metabolic heat production, insulation, and energetic constraints are heightened. We assessed thermoregulation in molting captive king penguins (<i>Aptenodytes patagonicus</i>) using simultaneous measurements of core and surface temperatures to test two hypotheses. Under the thermal challenge hypothesis, an initial rise in heat dissipation effort (i.e., increased peripheral vasomotion) followed by a rise in core temperature would indicate failure to prevent hyperthermia. Under the warm-up hypothesis, an initial rise of core temperature concomitant or followed by an increase in peripheral vasomotion would indicate regulated hyperthermia, possibly to accelerate feather development. Core and surface temperatures increased drastically but concomitantly during molt, providing tentative support to the warm-up hypothesis. Molting penguins did not pant, suggesting that peripheral heat dissipation was sufficient to regulate molting-induced hyperthermia. Core and subcutaneous temperatures in wild individuals resembled patterns measured in captivity, despite lower heat load and additional options for behavioral thermoregulation. These results indicate that hyperthermia is prevalent in molting king penguins, and documenting the timing of temperature changes provides novel insights for the molting physiology of penguins. Because molting-induced hyperthermia may contribute to heat load, we caution that molting may increase the susceptibility of wild penguins to heat stress, especially as regions near the poles warm at a disproportionately rapid rate.<b>NEW & NOTEWORTHY</b> Penguins may experience heat stress while molting, which causes increased metabolic heat generation and insulation. We assessed thermoregulation in molting captive king penguins (<i>Aptenodytes patagonicus</i>) using simultaneous measurements of core and surface temperatures. By measuring temperature throughout the entirety of the molt, we found that hyperthermia and increased peripheral heat dissipation are prevalent in molting king penguins. We caution that molting-induced hyperthermia may contribute to the susceptibility of penguins to heat stress in the wild.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R742-R752"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224674","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 stress response in the marine copepod, <i>Calanus finmarchicus</i>.","authors":"Sidonie Rousseau, Wassim Ameur, Elise Thiebaut, Tamer Hafez, Dag Altin, Bjørn Henrik Hansen, Kang Nian Yap","doi":"10.1152/ajpregu.00120.2025","DOIUrl":"10.1152/ajpregu.00120.2025","url":null,"abstract":"<p><p>As climate change intensifies, marine organisms face multiple environmental stressors that challenge their survival and adaptability. Oxidative stress occurs when environmental conditions deviate far from an organism's optimal range, and responses vary due to diverse molecular and physiological pathways. Stress responses can differ by sex and be influenced by multiple stressors, yet the underlying mechanisms remain poorly understood. This study examined sex differences in stress response in copepods <i>Calanus finmarchicus</i>, one of the most ecologically important animals in the marine ecosystem. Adult males and females were exposed to paraquat, an oxidative stress inducer, to assess survival, metabolic rate, and expression of antioxidant genes and chaperones. In addition, females were subjected to combined heat and paraquat stress to explore interactive effects on stress tolerance. Males exhibited greater upregulation of antioxidant enzymes but had lower survival than females in response to paraquat exposure. Despite similar metabolic rates between sexes, females were larger and had greater lipid sac volume than males, which may contribute to their higher resilience and survival under paraquat exposure. In females, combined paraquat and heat stress had a synergistic detrimental effect on survival but only heat stress impacted metabolic rate. In addition, heat stress modulated female's gene expression, antagonizing glutathione-S-transferase III and enhancing superoxide dismutase expression. A potential threshold for superoxide dismutase and catalase fold change was identified in paraquat-exposed females. Understanding the variability in stress responses is crucial for predicting species resilience to climate change and environmental disturbances, ultimately informing conservation and ecosystem management strategies.<b>NEW & NOTEWORTHY</b> This individual-based study reveals sex-specific differences in stress responses of the copepod <i>Calanus finmarchicus</i> to oxidative stress, with males showing higher sensitivity but no significant different metabolic strategies compared with females. It also identifies the antagonistic and synergistic effects of heat and paraquat-induced oxidative stress on antioxidant gene expression, and a potential maximum threshold for superoxide dismutase and catalase fold change in females.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R771-R783"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285373","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":"Moderate intermittent hypoxic conditioning to enhance cerebrovascular function in the elderly: a randomized controlled trial.","authors":"Hugo Randy, Titouan Paul Perrin, Abdallah Ghaith, Dario Kohlbrenner, Patrice Flore, Benoit Champigneulle, Michel Francois Guinot, Stéphane Doutreleau, Samuel Verges, Julien V Brugniaux, Mathieu Marillier","doi":"10.1152/ajpregu.00160.2025","DOIUrl":"10.1152/ajpregu.00160.2025","url":null,"abstract":"<p><p>Aging is associated with cerebrovascular impairment, increasing the risk for neurovascular and degenerative diseases. Intermittent hypoxic conditioning (IHC) has been proposed as a valuable strategy to enhance vascular health. However, its effects in cerebrovascular territories remain unclear, particularly in older adults. Eighteen elderly individuals (62-79 yr, 11 males) were randomly assigned to either an IHC (<i>n</i> = 8) or a control group (CTL, <i>n</i> = 10). Both groups underwent 24 sessions (3 sessions/wk) of passive moderate exposure to either intermittent hypoxia (targeted oxygen saturation by pulse oximetry = 75%-80%) or sham hypoxia. Middle cerebral artery (MCA) reactivity to hypo- (hyperventilation task) and hypercapnia (carbon dioxide ramp administration) was assessed using transcranial Doppler ultrasound. Cerebrovascular reactivity to carbon dioxide (CVR_CO2) was evaluated in both absolute and relative changes in MCA blood velocities (MCAv), before (Pre), 3-4 days after (post 1), and 2 mo after (post 2) intervention cessation. As expected, MCAv decreased during hypocapnia (CTL = -15.7 ± 7.0 cm/s; IHC = -15.9 ± 6.0 cm/s) and increased during hypercapnia (CTL = 20.7 ± 8.4 cm/s; IHC = 18.2 ± 11.1 cm/s) at all time points in both groups. However, compared with CTL, IHC did not significantly improve any CVR_CO2 parameters (e.g., relative CVR_CO2 to hypercapnia, Pre: CTL = 4.3 ± 1.9, IHC = 3.1 ± 2.0; post 1: CTL = 4.1 ± 1.6, IHC = 3.4 ± 1.6; post 2: CTL = 4.7 ± 2.0, IHC = 3.5 ± 1.7 cm/s/mmHg; <i>P</i> = 0.739). The present work does not support the potential benefits of IHC on cerebrovascular function. However, future studies are required to confirm these preliminary results and may consider a more comprehensive appraisal of the cerebral hemodynamic control.<b>NEW & NOTEWORTHY</b> This study is the first to investigate the effects of IHC on CVR_CO2 over the short- and mid-term in elderly individuals. Contrary to our initial hypothesis, 8 wk of moderate IHC did not enhance CVR_CO2 at any time point.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R805-R812"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336371","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":"Irisin deficiency exacerbates cardiac dysfunction and enhances hemorrhage injury in hemorrhage/resuscitation.","authors":"Supaporn Kulthinee, Lijiang Wang, John Slate-Romano, LingNa Huang, Thomas Zhao, Patrycja M Dubielecka, Jia-Qiang He, Shougang Zhuang, Ting C Zhao","doi":"10.1152/ajpregu.00013.2025","DOIUrl":"10.1152/ajpregu.00013.2025","url":null,"abstract":"<p><p>Irisin contributes critically to modulating metabolism and tissue survival in muscles and adipocytes. Whether deficiency of irisin impacts the hemorrhagic injury and/or whether the effect of irisin deficiency on hemorrhagic injury primarily relies on irisin, which is currently unknown. We use an irisin knockout mouse to eliminate irisin and pharmacological approaches in a mouse hemorrhagic model to determine the function of irisin on hemorrhage and resuscitation (H/R). Hemorrhage was induced by achieving a mean arterial blood pressure of 35-45 mmHg for 60 min, followed by 2 h of resuscitation in mice. Experimental groups were divided as follows (<i>n</i> = 6-8 per group): sham <i>groups I</i> and <i>II</i>: wild-type (WT) mice and irisin-knockout (KO) mice were subjected to femoral catheterization without H/R; <i>groups III</i> and <i>IV:</i> WT mice and irisin-KO mice were subjected to H/R, respectively; <i>groups V</i> and <i>VI</i>: irisin (50 μg/kg, iv) was infused into WT and irisin-KO H<i>/</i>R mice during resuscitation. Mean blood pressure, myocardial function, serum cytokine, inflammatory cell infiltration, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive apoptosis, active caspase 3, components of oxidative phosphorylation, and mitochondrial ATPase activity in muscles were determined. Irisin deficiency exacerbated cardiac dysfunction in H/R in association with increases in interleukin 6, the infiltration of inflammatory cells, active caspase-3, and reduced oxidative phosphorylation and ATPase activities. The effects of irisin deletion on H/R were rescued by irisin. Deletion of irisin exacerbated injury of H/R, which was rescued by infusion of irisin, suggesting a key role of irisin in the regulation of hemorrhage/resuscitation.<b>NEW & NOTEWORTHY</b> Deletion of irisin resulted in a reduction in cardiac function and hemodynamics and exacerbated inflammation and tissue injury in response to hemorrhagic injury. Irisin rescued the hemorrhage-induced cardiac depression and attenuated the inflammatory response induced by irisin deficiency in hemorrhagic injury, suggesting that irisin contributes critically to the protective role in hemorrhage/resuscitation.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R813-R825"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12699480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297775","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":"Longitudinal changes in cardiovascular and sympathetic neural responses to static handgrip exercise throughout pregnancy.","authors":"Takuro Washio, Sarah L Hissen, John D Akins, Ryosuke Takeda, Safia Khan, Andrew R Tomlinson, David B Nelson, Tony G Babb, Qi Fu","doi":"10.1152/ajpregu.00074.2025","DOIUrl":"10.1152/ajpregu.00074.2025","url":null,"abstract":"<p><p>The time-course changes in the exercise pressor response throughout gestation remain unknown. As pregnancy is associated with altered hemodynamics and sympathetic activation, we hypothesized that neural responses to static handgrip (SHG) exercise would be augmented, especially during late pregnancy. Forty-six women (30 ± 6 yr [SD]) were studied longitudinally during early and late pregnancy and postpartum. Mean arterial pressure (MAP), cardiac output (Qc), total peripheral resistance (TPR = MAP/Qc), and muscle sympathetic nerve activity (MSNA) were measured during supine rest and SHG at 40% of maximal voluntary contraction force until fatigue, followed by 2-min postexercise circulatory occlusion (PECO) to isolate muscle metaboreflex activation. The peak increase (Δ) in MAP during fatiguing SHG did not differ among gestation stages (<i>P</i> = 0.669), but ΔMAP during PECO trended smaller in late pregnancy than postpartum (<i>P</i> = 0.054). ΔQc during SHG and PECO was larger in late pregnancy compared to early pregnancy and postpartum (<i>P</i> < 0.05), while ΔTPR was lower in late pregnancy (<i>P</i> < 0.05). ΔMSNA during SHG was not different (<i>P</i> = 0.740) but smaller during PECO in late pregnancy compared to early pregnancy and postpartum (<i>P</i> < 0.05). Confounding factors like obesity or pregnancy complications did not affect these responses (<i>P</i> > 0.05). Sympathetic activation elicited by the muscle metaboreflex was reduced in late pregnancy, which may be related to the blunted peripheral vasoconstriction. Conversely, the cardiac output response to exercise was augmented in late pregnancy. These results suggest that central and peripheral responses are impacted differently to maintain an adequate pressor response to exercise throughout pregnancy, regardless of obesity and complications.<b>NEW & NOTEWORTHY</b> To our knowledge, this is the first longitudinal study to assess sympathetic neural responses during fatiguing static handgrip exercise across pregnancy. Our findings indicate that cardiovascular and sympathetic neural adaptations to exercise occur throughout pregnancy, regardless of the presence of obesity or pregnancy complications. Notably, central and peripheral mechanisms appear to be regulated differently, ensuring that an adequate pressor response to exercise is maintained during pregnancy and into the postpartum period.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R661-R672"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12668593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190676","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":"Cystathionine γ lyase deletion enhances corpus cavernosum contraction via thromboxane A₂ and neurogenic pathways without affecting endothelial function.","authors":"Tooyib A Azeez, Clifford J Pierre, Colin M Ihrig, Stephen P Chelko, Judy M Muller-Delp, Justin D La Favor","doi":"10.1152/ajpregu.00133.2025","DOIUrl":"10.1152/ajpregu.00133.2025","url":null,"abstract":"<p><p>Cystathionine γ-lyase (CSE) produces hydrogen sulfide (H₂S), a vasodilator critical for vascular function. Although its systemic effects are well-documented, its role in erectile physiology remains unclear. This study investigated the impact of CSE deletion on vascular and erectile tissue reactivity. We hypothesized that CSE knockout (CSE-KO) mice would exhibit endothelial dysfunction. A total of 22 CSE-KO and 22 age-matched wild-type (WT) controls were studied at 1 yr of age. The internal iliac artery (IIA), internal pudendal artery (IPA), and corpus cavernosum (CC) were harvested for ex vivo functional assessments using tissue, wire, and pressure myography. Vasoconstriction was evaluated using phenylephrine, endothelin-1, U-46619, and electrical field stimulation (EFS). Endothelium-dependent relaxation was assessed using acetylcholine (ACh) and flow-mediated dilation, whereas endothelium-independent relaxation was evaluated using sodium nitroprusside (SNP). Sodium sulfide (Na₂S) was used to assess H₂S-mediated dilation. Nonadrenergic, noncholinergic (NANC) transmission was evaluated using EFS. No significant differences were observed in ACh-, SNP-, or flow-mediated relaxation, although CSE-KO mice demonstrated impaired NANC-nerve-mediated relaxation in the CC. Moreover, CSE-KO mice exhibited significantly enhanced CC contraction in response to U-46619 and EFS, suggesting increased vascular resistance in the end-organ CC rather than the prepenile arteries. Histological analysis revealed no significant structural or fibrotic remodeling in any tissue, although there was a trend toward increased collagen deposition in the IIA and IPA. These findings indicate that chronic CSE deficiency does not impair endothelial function but alters neurogenic control and increases vasoconstrictive sensitivity specifically in the CC, potentially predisposing to erectile dysfunction.<b>NEW & NOTEWORTHY</b> This study highlights the critical role of hydrogen sulfide (H₂S) in erectile physiology by demonstrating that cystathionine γ-lyase (CSE) deletion does not impair endothelial function but significantly enhances neurogenic and thromboxane A₂ receptor-induced vasoconstriction specifically in the corpus cavernosum (CC). These findings suggest that endogenous H₂S modulates neurovascular control of erection. Its deficiency predisposes the erectile system to heightened vascular resistance predominantly in the end organ, providing novel insights into the vascular mechanisms underlying erectile dysfunction.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R715-R726"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022708","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":"Nonphotic entrainment and phase shifting of circadian rhythms by novelty-induced wheel running in female mice.","authors":"Ren Y Sato, Yujiro Yamanaka","doi":"10.1152/ajpregu.00194.2025","DOIUrl":"10.1152/ajpregu.00194.2025","url":null,"abstract":"<p><p>Environmental light-dark (LD) cycles serve as the primary zeitgeber for the mammalian circadian system, but scheduled physical activity such as voluntary wheel running can act as a potent nonphotic cue. Previous studies on nonphotic entrainment have predominantly used male animals, leaving sex-specific mechanisms largely unexplored. In this study, we investigated circadian behavioral entrainment and phase-shifting responses to scheduled wheel-running activity in female C57BL/6J mice under constant darkness (DD). Mice underwent scheduled daily exposure to a novel cage with a running wheel (NCRW) for 3 h, and spontaneous locomotor rhythms were analyzed before, during, and after exposure. Fifteen of 16 female mice achieved steady-state entrainment when the NCRW schedule coincided with activity onset. However, they lacked both anticipatory behavior and behavioral aftereffects of entrainment-defined as persistent changes in circadian period and activity timing following entrainment-unlike what has been previously reported in males. To interpret entrainment dynamics, we constructed phase response curve (PRC) for a single 3-h pulse of exposure to NCRW in both sexes. Female PRC displayed prominent delay portions in the late subjective day and early subjective night, contrasting with male profiles showing minor advances in the same windows. These findings reveal a sex difference in nonphotic circadian entrainment and suggest that underlying mechanisms, including oscillator coupling or differential sensitivity to nonphotic stimuli, may vary between males and females. The results emphasize the importance of considering biological sex in circadian research and provide a basis for further investigation into sex-specific regulation of behavioral rhythms.<b>NEW & NOTEWORTHY</b> This study reveals sex-specific differences in nonphotic circadian entrainment induced by scheduled wheel-running activity in mice. Female mice exhibited distinct phase response curves and lacked behavioral aftereffects, contrasting with previously reported male patterns. These findings highlight the importance of biological sex in circadian regulation and suggest that nonphotic entrainment mechanisms may differ fundamentally between sexes.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R796-R804"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336422","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":"Cerebral pressure-flow relationship directional sensitivity in healthy lowlanders and natives at high altitude.","authors":"Shahrzad Soleimani Dehnavi, Jonathan D Smirl, Marc-Antoine Roy, Lawrence Labrecque, François Billaut, Kurt J Smith, Samuel J E Lucas, Philip N Ainslie, Patrice Brassard","doi":"10.1152/ajpregu.00151.2025","DOIUrl":"10.1152/ajpregu.00151.2025","url":null,"abstract":"<p><p>Whether cerebral pressure-flow relationship directional sensitivity, which represents the attenuated changes in cerebral blood velocity in response to transient increases, compared with decreases, in mean arterial pressure (MAP), is altered in lowlanders at high altitude or differs between lowlanders and Sherpa (a well-adapted highlander population of the Nepalese Khumbu region) is unknown. Both MAP and middle cerebral artery mean blood velocity (MCAv) were recorded continuously during 5-min repeated squat-stands (RSS) at 0.05 Hz and 0.10 Hz at sea level (<i>n</i> = 10), initial exposure to high-altitude (<i>n</i> = 8), after 2 wk of partial acclimatization to high-altitude (<i>n</i> = 9), and in Sherpa (<i>n</i> = 16). For each transition, we calculated absolute and relative MCAv and MAP changes with respect to the transition time intervals of both variables indexing time adjusted ratios when MAP increases (ΔMCAv_T/ΔMAP_T^INCREASE and %MCAv_T/%MAP_T^INCREASE) and decreases (ΔMCAv_T/ΔMAP_T^DECREASE and %MCAv_T/%MAP_T^DECREASE). Regardless of altitude conditions, %MCAv_T/%MAP_T^INCREASE was lower than %MCAv_T/%MAP_T^DECREASE [0.05 Hz RSS: (<i>P</i> = 0.007); 0.10 Hz RSS (<i>P</i> = 0.003)] in lowlanders. Partially acclimatized lowlanders and Sherpa had lower %MCAv_T/%MAP_T^INCREASE than %MCAv_T/%MAP_T^DECREASE at 0.05 Hz (<i>P</i> = 0.007), but comparable metrics at 0.10 Hz RSS (<i>P</i> = 0.971). These findings indicate acute exposure and partial acclimatization to high altitude do not alter the cerebral pressure-flow relationship directional sensitivity compared with sea level measures in lowlanders. In addition, the hysteresis-like pattern in Sherpa is not different when compared with partially acclimatized lowlanders.<b>NEW & NOTEWORTHY</b> Cerebral blood flow changes are buffered when blood pressure increases versus decreases. The current findings suggest that acute exposure and partial acclimatization to high altitude do not influence the presence of this phenomenon in lowlanders. Preservation of this hysteresis-like pattern across all altitude conditions may protect the cerebral microvasculature from hypoxia-induced increases in blood pressure. However, cerebral pressure-flow directional sensitivity is absent in Sherpa, a well-adapted highlander population, when blood pressure oscillates at higher frequency.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R727-R741"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197957","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":"Defining human thermoregulation limits: a critical evaluation of predictive models using healthy young adults.","authors":"Faming Wang, Huijuan Xu, Tze-Huan Lei, Yi Xu, Haojian Wang, Lijuan Wang","doi":"10.1152/ajpregu.00108.2025","DOIUrl":"10.1152/ajpregu.00108.2025","url":null,"abstract":"<p><p>The core temperature inflection point (CTIP) method (also known as humidity-ramp protocol) and biophysical modeling are widely used to determine human thermoregulation limits, yet their validity under prolonged heat exposure remains unverified. This study evaluated the predictive accuracy by exposing 36 healthy young adults (20 males and 16 females) to five counterbalanced 8-h indoor heat trials in a controlled chamber (36°C/74.5%RH, 40°C/55.0%RH, 44°C/29.2%RH, 47°C/35.6%RH, and 50°C/24.5%RH). These conditions were selected based on prior CTIP and biophysical model predictions of human thermoregulation limits. Participants engaged in sedentary office tasks (1.29-1.67 METs), wore standardized summer clothing (0.39-0.40 clo), and had ad libitum access to an electrolyte drink, with a 500-kcal sandwich provided at midday. Rectal temperature (<i>T</i>_rec) was continuously monitored. Contrary to model predictions, all five conditions remained compensable (<i>T</i>_rec rise rate ≤ 0.1°C/h), with mean peak <i>T</i>_rec well below heatstroke thresholds (38.2 ± 0.4°C). At 44°C/29.2%RH, females exhibited significantly lower <i>T</i>_rec than males (<i>P</i> < 0.05); however, no sex differences in steady-state <i>T</i>_rec responses were observed across other conditions (all <i>P</i> > 0.10). All exposures were compensable, aligning with the broader literature indicating minimal sex-based variability under such conditions. Collectively, CTIP and biophysical models substantially underestimated human thermoregulation limits, leading to overpredicted heat risk across all trials. These findings challenge the reliability of current predictive methods, suggesting human tolerance may exceed existing estimates. Refining these models is essential for improving heat risk assessment and informing public and occupational health guidelines in a warming climate.<b>NEW & NOTEWORTHY</b> This study reveals that widely used methods-core temperature inflection point and biophysical models-substantially underestimate human thermoregulation limits during prolonged heat exposure. Despite predictions of uncompensable heat stress, all five 8-h trials remained compensable, with core temperatures well below critical thresholds. These findings challenge the accuracy of current predictive tools and highlight the need to refine models to better assess heat risk in real-world, prolonged exposure scenarios.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R524-R533"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938990","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":"Unraveling the enterohepatic paradigm in sleeve gastrectomy: bile acids lead, microbiome follows.","authors":"Gopala Koneru, Lama Noureddine, Mohamad Mokadem","doi":"10.1152/ajpregu.00204.2025","DOIUrl":"10.1152/ajpregu.00204.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R586-R588"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12633759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079463","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}