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

{"title":"Core temperature responses during passive heat exposure differentiate mice previously exposed to exertional heat stroke and endotoxemia.","authors":"Francisco Teixeira-Coelho, Sebastian Cabrera, Zhuoxin Li, Ali Aldakkan, Gisienne Reis, Michele Moraes, Orlando Laitano","doi":"10.1152/ajpregu.00182.2026","DOIUrl":"10.1152/ajpregu.00182.2026","url":null,"abstract":"<p><p>Exertional heat stroke (EHS) induces thermoregulatory and inflammatory disturbances, yet whether core temperature (Tcore) responses are altered during subsequent passive heat exposure (PHE) remains unknown. Our purpose was to determine whether prior exposure to EHS or lipopolysaccharide (LPS)-induced systemic inflammation alters Tcore response during a subsequent PHE in mice. Receiver operating characteristic (ROC) curve assessment was performed as a secondary analysis to establish the ability of the Tcore response to discriminate animals previously exposed to EHS or LPS. Thirty-one female mice were assigned to three groups: control (CON), LPS, or EHS. Animals were implanted with a Tcore telemetry sensor. Three hours before the PHE, mice in the LPS group received a single intraperitoneal injection of LPS (100 µg·kg^-1), whereas 24 h before the PHE, EHS mice underwent an EHS protocol at 37.5°C and 40% relative humidity. CON animals received no intervention. The PHE test consisted of 40 min exposure to a 40°C environment with Tcore continuously recorded. During PHE, EHS mice exhibited higher Tcore than CON and LPS mice at 10 min (CON: 39.7 ± 0.2°C; LPS: 39.4 ± 0.4°C; EHS: 40.6 ± 0.3°C; <i>P</i> < 0.001) and 20 min (<i>P</i> < 0.001). After 30 min, both EHS and LPS groups displayed higher Tcore relative to CON. ROC curve analysis demonstrated that a Tcore threshold of 40.8°C at 10 min yielded 69% sensitivity and 94% specificity for identifying prior EHS (<i>P</i> < 0.001). These findings demonstrate that prior EHS and LPS alter the Tcore response during subsequent PHE in mice.<b>NEW & NOTEWORTHY</b> Prior exertional heat stroke (EHS) altered core temperature (Tcore) responses during subsequent passive heat exposure (PHE) in mice. Systemic inflammatory stress induced by lipopolysaccharide (LPS) also altered Tcore, although with a distinct temporal profile compared with EHS. These findings demonstrate that both serious heat illness and inflammatory stress can disrupt Tcore responses during environmental heat exposure and establish a foundation for future mechanistic studies investigating recovery following physiological stress in mice.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R576-R582"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975214","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":"Diet Composition Modifies Cardiometabolic Phenotype Development in the 4-Vinylcyclohexene Dioxide (VCD) Ovarian Failure Model of Menopause.","authors":"Natalia M Mathieu, Samuel B R Lawton, Margaret M Dorrington, Connie C Grobe, Valerie W Hole, Kelsey K Wackman, Henry Bordas-Murphy, Julie K Freed, Jeffrey L Segar, Pablo Nakagawa, Curt D Sigmund, Gary C Mouradian, Justin L Grobe, John J Reho","doi":"10.1152/ajpregu.00321.2025","DOIUrl":"10.1152/ajpregu.00321.2025","url":null,"abstract":"<p><p>In humans, menopause is associated with a suppression of resting metabolic rate (RMR), accelerated adipose gains, and increased risk of cardiometabolic disease. Mechanistic dissection of the changes in RMR control across the menopause transition is difficult because rodent models do not naturally undergo menopause. Although rodents lack a natural menopause, chemical treatment with 4-vinylcyclohexene diepoxide (VCD) induces progressive ovarian failure, paralleling the complex hormonal alterations across perimenopause and menopause that occur in humans. To explore the impact of diet upon cardiometabolic phenotype development in this experimental model of menopause, young adult (10-12wk old) female C57BL/6J mice were fed either PicoLab 5L0D (corn/soy-based, phytoestrogen-containing) or Inotiv 2920x (wheat/corn-based, phytoestrogen-free) diets and treated with VCD (160mg/kg/d for 20d) or sesame oil vehicle. In mice fed 5L0D, VCD caused a reduction in RMR and thereby total energy expenditure which was followed by exaggerated adipose gains, despite no changes in food intake. In contrast, in mice fed 2920x, VCD modestly suppressed activity-dependent expenditure but had no effects on RMR, food intake, or adiposity. VCD had no significant modulatory effects upon sodium intake behaviors, digestive efficiency, or endothelial-dependent vascular relaxation in mice fed either diet, though diet alone did influence these endpoints. Together, these findings demonstrate that diet composition significantly modifies the development of cardiometabolic phenotypes in the VCD rodent model of menopause. Future studies utilizing VCD-induced ovarian failure in rodents to model menopause must carefully consider the modulatory effect of diet formulation upon phenotype development, and thereby the translational relevance of results.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103070","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":"A method for direct measurement of afferent renal nerve activity in unanesthetized rats.","authors":"Mohammed H Abdulla, Edward J Johns","doi":"10.1152/ajpregu.00275.2025","DOIUrl":"10.1152/ajpregu.00275.2025","url":null,"abstract":"<p><p>This study introduces a novel method for recording afferent renal nerve activity (ARNA) in unanesthetized rats. A bipolar electrode was surgically implanted on the left renal nerve to record renal nerve activity (RNA), and efferent renal nerve activity (ERNA) was selectively blocked by administering 5% lidocaine via a polyurethane catheter placed over the renal artery-aorta junction. Lidocaine administration reduced RNA by approximately 82% relative to prelidocaine values, enabling the isolation of afferent nerve signals. Intrarenal arterial infusion of increasing doses of bradykinin (10, 20, 40, and 80 µg/kg) following lidocaine infusion produced a significant increase in ARNA, confirming preserved afferent function. This demonstrates the feasibility of this approach for investigating renorenal reflexes and the dynamic interplay between ARNA and ERNA, with implications for understanding homeostatic regulation and the pathophysiology of conditions such as hypertension and kidney disease.<b>NEW & NOTEWORTHY</b> This is the first method to enable real-time, selective measurement of ARNA in unanesthetized rats without interference from efferent signals. The use of targeted lidocaine administration allows functional separation of afferent and efferent components of renal nerve activity in vivo. This technique provides a tool to study renorenal reflexes under physiological and pathophysiological conditions, advancing our understanding of autonomic regulation in health and disease.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R511-R523"},"PeriodicalIF":2.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838950","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":"Ketone monoester intake affects the ventilatory response to O₂ and CO₂ in healthy individuals at high altitude.","authors":"Myrthe Stalmans, Domen Tominec, Benjamin J Narang, Giorgio Manferdelli, Gregoire P Millet, Tadej Debevec, Chiel Poffé","doi":"10.1152/ajpregu.00073.2026","DOIUrl":"https://doi.org/10.1152/ajpregu.00073.2026","url":null,"abstract":"<p><p><b>Introduction.</b> Both cerebral blood flow (CBF) and ventilation (V̇_E) respond to systemic O₂ and CO₂ levels. Ketone ester (KE) ingestion elicits hyperventilation, thereby increasing blood oxygenation in hypoxia while reducing blood buffering capacity and inducing hypocapnia-mediated CBF reductions. We aimed to characterize the impact of KE on V̇_E and CBF at terrestrial altitude, as well as their reactivity to O₂ and CO₂ (V̇_ER and CVR, respectively). <b>Methods.</b> Thirty-four participants performed a double-blind, placebo-controlled study consisting of a normoxic and a hypobaric hypoxic session. The latter was performed after 20 h at terrestrial altitude (3,375 m). While no supplements were provided at sea level, the altitude session involved regular ingestion of KE or placebo drinks. Middle cerebral artery velocity (MCAv) was measured using transcranial Doppler ultrasonography. Using a steady-state protocol, V̇_ER and CVR were calculated as respectively V̇_E or MCAv per [end-tidal CO₂ pressure (P_ETCO₂)] while breathing ambient air (<i>i.e.</i>, baseline stage), 3% or 6% hyperoxic CO₂, or during hyperventilation-induced hypocapnia. Blood acid-base balance was evaluated from an arterialized capillary blood sample. <b>Results.</b> KE intake increased blood [β-hydroxybutyrate] and reduced blood pH, arterial CO₂ partial pressure, and bicarbonate concentrations. KE induced hyperventilation and reduced V̇_ER, mostly originating from the baseline-to-3%-CO₂ transition. KE did not affect MCAv or CVR. <b>Conclusions.</b> The effect of KE on V̇_ER presumably resulted from hyperventilation while breathing ambient air, rather than reflecting altered V̇_ER to O₂ and CO₂, but the underlying mechanisms remain uncertain. Despite acid-base dysregulations with KE intake, cerebrovascular outcomes remained unaltered.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030030","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":"Nutrient restriction dynamically alters glucose tolerance and ceramide concentrations in periparturient ewes.","authors":"Miranda J Farricker, Josie L Judge, Andrew Smith, Shalise T Hill, Pragney Deme, Norman J Haughey, Joseph W McFadden, Amanda N Davis","doi":"10.1152/ajpregu.00098.2026","DOIUrl":"https://doi.org/10.1152/ajpregu.00098.2026","url":null,"abstract":"<p><p>The periparturient period in mammals is characterized by reduced insulin action, which allows nutrient partitioning to support fetal growth and milk synthesis. The sphingolipid ceramide is an established interrogator of insulin signaling in non-ruminants and accumulates during this period in dairy cows. We investigated the effects of short-term nutrient restriction (NR) on glucose tolerance and ceramide metabolism in multiparous ewes (n = 19) during this period. Ewes were fed ad libitum or subjected to two 5-d 50% NR periods in late gestation and early lactation. NR reduced circulating glucose and insulin and increased fatty acids, consistent with negative energy balance. Milk yield was lowered by lactational NR; however, production efficiency improved. Serial intravenous glucose tolerance tests revealed impaired glucose tolerance following gestational NR that was sustained across lactation, evidenced by greater glucose and fatty acid area-under-the-curves regardless of insulin secretion. Most plasma and milk ceramide subclasses were highly abundant in C24:0 and C24:1 acyl moieties; however, plasma lactosylceramide was differentially enriched with C16:0 and C20:1. NR induced biphasic shifts in plasma ceramide species and subclasses across the periparturient period, with peak ceramide and hexosylceramide species concentrations in early lactation prior to the second NR and opposite patterns in lactosylceramides. Milk ceramide and hexosylceramide profiles were distinct from plasma; however, lactosylceramide species responded similarly. Plasma lactosylceramide species also had a strong negative correlation to milk yield. Overall, NR induced coordinated endocrine, metabolic, and sphingolipid adaptations in periparturient ewes, implicating ceramides as potential mediators of metabolic regulation during this critical physiological transition.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023459","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":"Cerebrovascular Responses to Aerobic Exercise in Young Healthy non-Hispanic Black and White Males.","authors":"Ziba Taherzadeh, Taha A Alhalimi, Zachary R Oldham, Claire E Kissell, Benjamin E Young, Paul J Fadel","doi":"10.1152/ajpregu.00177.2026","DOIUrl":"https://doi.org/10.1152/ajpregu.00177.2026","url":null,"abstract":"<p><p>Non-Hispanic Black (BL) adults experience a higher burden of cerebrovascular disease compared with other racial and ethnic groups, for which impaired cerebrovascular function is a well-established risk factor. Previous studies have shown that at rest, cerebrovascular function is lower in young BL adults compared with young WH adults. However, cerebrovascular responses to exercise have never been investigated in BL adults. We hypothesized that young BL males would exhibit attenuated cerebrovascular responses to aerobic exercise compared with their WH counterparts. Cerebrovascular (i.e., middle cerebral artery mean blood velocity; MCAvmean, cerebrovascular conductance index; CVCi and cerebral pulsatility index; PI), cardiovascular (i.e., brachial blood pressure and heart rate), and respiratory (i.e., VO₂ and CO₂) variables were measured at rest and during incremental and steady-state semi-recumbent cycling exercise in 13 BL and 11 WH males. At rest there were no differences between groups for cerebrovascular, cardiovascular and respiratory measures (all p>0.05). Groups were also comparable for cardiorespiratory fitness (VO₂peak, BL:39.5±5.1 vs WH:39.7±6.2 mL/kg/min, p=0.92). During exercise, MCAvmean increased similarly in both groups for both incremental (intensity:p<0.01, race: p=0.44, interaction: p=0.57; e.g., at 50%VO₂peak, BL: ∆16.2±4.3 vs WH: ∆15.7±8.7 cm/s) and steady-state (intensity:p<0.01, race: p=0.45, interaction: p=0.98; e.g., at 50 watts, BL: ∆5.8±2.3 vs WH: ∆4.8±5.0 cm/s) exercise. There was also no main effect of race for CO₂, CVCi or PI during either exercise protocol (all p>0.05). Thus, contrary to our hypothesis, no detectable racial differences in cerebrovascular responses to incremental or steady-state aerobic exercise were found in this cohort of young, otherwise healthy males.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023476","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":"Hidden Overshoot in Cerebral Blood Flow: Implications for Accurate Assessment of Cerebral CO₂ Reactivity.","authors":"Shigehiko Ogoh, Marina Feeley, Narumi Kunimatsu, Jiayu Liu, Keisho Katayama, Tadayoshi Miyamoto","doi":"10.1152/ajpregu.00056.2026","DOIUrl":"https://doi.org/10.1152/ajpregu.00056.2026","url":null,"abstract":"<p><p>The impact of temporal and individual differences in respiratory and cerebrovascular responses on the assessment of cerebrovascular carbon dioxide (CO₂) reactivity (CVR) using the Douglas bag method remains unclear. We hypothesized that accurate CVR assessment requires attaining a respiratory steady-state during CO₂ inhalation, followed by stabilization of middle cerebral artery mean blood velocity (MCA V_mean), mediated by changes in arterial CO₂ tension. To test this hypothesis, we conducted three 8-minute CO₂ inhalation trials (at 0%, 3.5%, and 5%) and analyzed minute-by-minute responses in 32 healthy participants. Twelve participants (37.5%) exhibited an overshoot in MCA V_mean immediately after the onset of CO₂ inhalation. When averaged across all participants, CVR reached an apparent steady-state within 2-3 minutes. In contrast, in the overshoot group, MCA V_mean increased acutely and thereafter decreased toward a plateau at approximately 6-7 minutes, whereas ventilation increased progressively throughout the exposure. The magnitude of the MCA V_mean overshoot was significantly associated with central respiratory chemoreflex sensitivity (r = 0.560, P = 0.0009), but not with CVR (r = -0.206, P = 0.258). These findings indicate that inter-individual variability in CVR estimates obtained using the Douglas bag method may be attributable to inter-individual differences in cerebrovascular regulation arising from respiratory responses to CO₂ inhalation. Consequently, assessing CVR during the early phase of CO₂ inhalation may over- or underestimate steady-state cerebrovascular responsiveness because of inter-individual differences in respiratory or cerebrovascular control. Accordingly, we recommend a minimum CO₂ inhalation duration of 6-7 minutes to ensure attainment of a steady-state when assessing CVR.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149011812","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":"Changes in IMCL content and storage characteristics during an acute bout of high-intensity interval exercise are influenced by sex and muscle fiber type.","authors":"Megan M Lo, Kayleigh M Beaudry, Claire Woodgate, Michaela C Devries","doi":"10.1152/ajpregu.00282.2025","DOIUrl":"10.1152/ajpregu.00282.2025","url":null,"abstract":"<p><p>Recently it was reported that intramyocellular lipids (IMCL) do not contribute to energy production during high-intensity interval exercise (HIIE) in males. However, females rely to a greater extent on lipid during moderate-intensity exercise compared with males, thus perhaps IMCL contribute to energy production during HIIE in females. The purpose of this study is to determine whether sex influences IMCL use or IMCL storage characteristics during an acute bout of HIIE. Young, healthy, recreationally active males (<i>n</i> = 12) and females (<i>n</i> = 12) performed an acute bout of HIIE (10 × 1 min at 90%HRmax) with biopsies taken from vastus lateralis prior to and following exercise for electron microscopic determination of IMCL storage and Western blot analysis of proteins related to lipid and aerobic metabolism. Total energy expenditure and relative contributions of fat and carbohydrate oxidation were determined using indirect calorimetry. Though carbohydrate oxidation was greater in males (males: 2.49 g/min, females: 1.69 g/min, <i>P</i> < 0.0001) during exercise, there were no sex differences in fat oxidation (males: 0.045 g/min, females: 0.049 g/min, <i>P</i> = 0.99). Sex influenced changes in the peripheral intermyofibrillar (IMF) region of type II fibers with IMCL content decreasing by 28% in females but increasing by 26% in males (<i>P</i> = 0.049), whereas the proportion of IMCL-mitochondria apposition increased by 26% in females compared with only 3% in males (<i>P</i> = 0.03). We also report differences in the change in IMCL morphology that are consistent with altered IMCL handling and mitochondrial interaction in females. We identify novel, sex-specific changes in IMCL content, apposition with mitochondria and morphology during an acute bout of HIIE.<b>NEW & NOTEWORTHY</b> To our knowledge, this is the first study to comprehensively examine sex-based differences in changes in intramyocellular lipid (IMCL) content, morphology, and mitochondrial interaction following acute high-intensity interval exercise (HIIE). We report that sex influences changes in IMCL content, morphology, and apposition with mitochondria during HIIE. Our findings provide novel microscopic insights into sex-specific IMCL organization and mitochondrial interaction during HIIE, and highlight the importance of considering sex in investigations of skeletal muscle metabolism.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R347-R363"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148373765","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 days of warm water immersion modulate baseline fluid-regulatory hormones without altering acute multisystem physiological stress responses in older males.","authors":"Ben J Lee, James J McCormick, Kelli E McCormick, Kristina-Marie T Janetos, Glen P Kenny","doi":"10.1152/ajpregu.00099.2026","DOIUrl":"10.1152/ajpregu.00099.2026","url":null,"abstract":"<p><p>Older adults exhibit heightened vulnerability to heat-related morbidity, yet it remains unclear whether short-term heat acclimation modifies integrative physiological stress responses in aging. We tested whether 7 days of passive heat acclimation via warm water immersion alters basal concentrations and acute exercise-heat stress responses of biomarkers reflecting fluid regulation, gastrointestinal epithelial integrity, renal stress, and inflammation in older males. Twelve habitually active older males (median [interquartile range] age: 68 [64-73] yr; [Formula: see text]: 34.1 [29.4-36.1] mL O₂·kg^-1·min^-1) completed an exercise-heat stress test before and after 7 consecutive days of warm water immersion (∼40°C), with rectal temperature maintained at ∼38.5°C for the final 60 min. Blood samples were collected before and after each exercise-heat stress test and analyzed using linear mixed-effects models (day × time). Repeated warm water immersion increased resting renin by 68% [95% confidence interval: 29, 120; <i>P</i> < 0.001], whereas neutrophil gelatinase-associated lipocalin and lipopolysaccharide-binding protein decreased by 24% [-40, -4; <i>P</i> = 0.023] and 22% [-37, -3; <i>P</i> = 0.026], respectively. Exercise-heat stress increased aldosterone by 45% [12, 87%; <i>P</i> = 0.004], renin by 41% [8, 84%; <i>P</i> = 0.01], intestinal fatty acid-binding protein by 52% [26, 85%; <i>P</i> < 0.001], and plasma osmolality by 5.6% [2.5, 8.7%; <i>P</i> < 0.001]. However, there was no day × time interaction for any biomarker (all <i>P</i> > 0.05), indicating that 7 days of warm water immersion did not alter the magnitude of the exercise-heat stress response. Short-term passive heat acclimation in older males induces selective fluid-regulatory endocrine adaptations consistent with preserved renin-angiotensin-aldosterone system plasticity, whereas gastrointestinal and renal stress responses to exercise-heat exposure remain unchanged.<b>NEW & NOTEWORTHY</b> This study demonstrates that short-term (7 days) passive heat acclimation via warm water immersion induces selective endocrine adaptation without uniform protection across physiological systems in older males aged 60-80. Although RAAS-mediated fluid regulation was modified following heat acclimation, gastrointestinal and renal stress responses to acute heat exposure persisted. These findings suggest that physiological adaptation to repeated heat exposure in aging may be compartmentalized across organ systems, with implications for vulnerability during extreme heat events.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R364-R375"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629375","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":"Systematic understanding of acute effects of dexmedetomidine on rat carotid sinus baroreflex-mediated sympathetic arterial pressure regulation.","authors":"Midori Kakuuchi, Toru Kawada, Nana Hiraki, Masafumi Fukumitsu, Kei Sato, Taichi Ando, Kazunori Uemura, Yoshihiro Muragaki, Kunihiko Kiuchi, Joe Alexander, Keita Saku","doi":"10.1152/ajpregu.00150.2026","DOIUrl":"10.1152/ajpregu.00150.2026","url":null,"abstract":"<p><p>Dexmedetomidine (DEX) is a centrally acting α₂-adrenergic agonist widely used for sedation in emergency and intensive care settings. We examined the effects of DEX on baroreflex-mediated sympathetic regulation of arterial pressure (AP) to distinguish its central and peripheral effects. In anesthetized male Wistar-Kyoto rats (<i>n</i> = 8), baroreflex-mediated changes in sympathetic nerve activity (SNA), AP, and heart rate (HR) were evaluated before and after intravenous DEX administration. DEX (2.5 μg/kg) significantly reduced the response ranges of AP (64.4 ± 9.2 to 5.8 ± 3.0 mmHg; <i>P</i> < 0.001), HR (46.5 ± 23.2 to 5.0 ± 6.2 beats/min; <i>P</i> = 0.003), and SNA (87.0 ± 7.5% to 12.6 ± 8.2%; <i>P</i> < 0.001). DEX also decreased the lower limits of HR (325.9 ± 14.6 to 302.2 ± 16.3 beats/min; <i>P</i> < 0.001) and SNA (14.6 ± 6.1% to 1.8 ± 3.0%; <i>P</i> = 0.037) but increased the lower limit of AP (65.4 ± 7.5 to 72.6 mmHg; <i>P</i> = 0.026). Furthermore, DEX reduced both the operating-point AP and gain. Peripheral effects contributed to an increase in operating-point AP (61.7 ± 9.1 vs. 80.9 ± 9.7 mmHg; <i>P</i> = 0.045) but did not affect operating-point gain (0.05 ± 0.08 vs. 0.05 ± 0.08; <i>P</i> = 0.859). In summary, DEX markedly suppressed SNA and induced peripheral vasoconstriction. These peripheral effects contributed to increased minimal AP and preservation of operating-point AP. However, the operating-point gain was substantially reduced, suggesting that AP stability in response to exogenous disturbances may be compromised under DEX sedation.<b>NEW & NOTEWORTHY</b> Dexmedetomidine profoundly reshapes baroreflex control beyond its sedative effects. In rats, it markedly reduced the response ranges of arterial pressure, heart rate, and sympathetic nerve activity, while increasing the minimum arterial pressure, a finding consistent with peripheral vasoconstriction. Although these peripheral effects helped preserve operating-point arterial pressure, baroreflex gain was substantially attenuated, suggesting that arterial pressure stability against exogenous disturbances may be compromised during dexmedetomidine sedation.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R427-R434"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688386","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}