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

{"title":"Molecular shifts induced by pseudohypoxia in gray seal blubber: an ex vivo approach.","authors":"Laura Oller, Joel Rocha, Holly Clare Armstrong, Simon E W Moss, Ailsa J Hall, Kimberley Ann Bennett","doi":"10.1152/ajpregu.00265.2025","DOIUrl":"10.1152/ajpregu.00265.2025","url":null,"abstract":"<p><p>The ability to withstand low and fluctuating oxygen levels is important for adipose tissue function. Hypoxia in mammalian cells typically stabilizes hypoxia<b>-</b>inducible factor (HIF-1α) that alters downstream structural and metabolic pathways, which can have pathological consequences in humans and rodents. Gray seals (<i>Halichoerus grypus</i>) have extensive subcutaneous adipose as blubber, which naturally undergoes oxygen restriction acutely during diving and chronically during fattening. This study explored how blubber regulates responses to chemically induced pseudohypoxia. We obtained blubber biopsies from weaned pups (<i>n</i> = 6) and prepared explants that we incubated with or without cobalt chloride (CoCl₂), which stabilizes HIF-1α under normoxia. One explant per animal was immediately snap-frozen, and the remaining explants and media were collected every 2 h. HIF-1α protein accumulation occurred rapidly in both control and CoCl₂-treated explants, peaking at 4 h and 2 h, respectively. <i>HIF-1α</i> mRNA increased in all explants. Mitochondrial complex I abundance increased in controls. CoCl₂ drove an additional increase in complex I, II, and V proteins compared with controls at all time points. Surprisingly, <i>Adiponectin</i> and <i>Ppar-γ</i> were not downregulated. <i>Collagen VI</i> abundance increased 6 h after treatment. Our results suggest that blubber explants experience hypoxia in culture, which is enhanced by chemical pseudohypoxia: CoCl₂ produced an additional impact on mitochondrial complex proteins. HIF-1α elevation in response to hypoxic challenge occurred earlier, to a greater extent but was shorter lived than in other mammalian adipose. Our findings highlight potential differences in responses of seal blubber to hypoxia compared with human and rodent adipose.<b>NEW & NOTEWORTHY</b> The molecular response to low oxygen in blubber had not been previously documented. This study showed a faster, but sustained, increase in molecular markers of hypoxia. It documents downstream molecular responses to those hypoxia-induced changes, revealing important adaptations in mechanisms that induce and sustain the hypoxia response in blubber. The exploration of natural vs. chemically reduced oxygenation in gray seal blubber suggests they induce contrasting mechanisms in the regulation of downstream effects of hypoxia.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R317-R335"},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802991","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 cocoa ingestion decreases spontaneous cardiac baroreflex sensitivity in healthy older adults.","authors":"Mami Hamaoka, Mary E J Lott, Zoe Eckman, Urs A Leuenberger, Cheryl Blaha, Takuto Hamaoka, Jonathan Carter Luck, Lawrence I Sinoway, Jian Cui","doi":"10.1152/ajpregu.00203.2025","DOIUrl":"10.1152/ajpregu.00203.2025","url":null,"abstract":"<p><p>Prior reports suggested the beneficial effects of cocoa intake on cardiovascular system. However, the effects of cocoa on cardiac baroreflex sensitivity (CBRS) remain poorly understood. In this study, we hypothesized that cocoa ingestion would increase CBRS in a dose-dependent manner. Seventeen healthy older adults (61 ± 8 yr; 8 M, 9 F) participated in five trials using 250-mL drinks containing 0, 2, 5, 13, or 26 g of cocoa, whereas the drinks had a similar appearance and taste. The trials were conducted in a randomized, double-blind design, at the same time each morning, with at least 72 h between sessions. Two hours after ingesting the experimental drink, beat-by-beat heart rate (HR) and blood pressure (BP) were recorded in a supine position. Spontaneous CBRS was calculated from the beat-by-beat systolic BP and RR interval data using a sequence method. There were no significant differences in BP and HR after ingesting the drink across all visits (repeated-measures ANOVA; <i>P</i> > 0.05). Cocoa ingestion dose-dependently decreased CBRS (repeated-measures ANOVA, <i>P</i> = 0.009). CBRS was significantly lower following 26 g of cocoa compared with 0 g (12.1 ± 5.7 vs. 18.2 ± 7.7 ms/mmHg, post hoc test, <i>P</i> = 0.018). In addition, CBRS was significantly and negatively correlated with cocoa dose (<i>R</i> = -0.35, <i>P</i> = 0.003). The data suggest that acute cocoa ingestion dose-dependently reduces CBRS in healthy older adults. As reduced CBRS may be associated with increased cardiovascular risks, this potential effect of cocoa warrants attention despite its known cardiovascular benefits.<b>NEW & NOTEWORTHY</b> Evidence suggests that regular consumption of cocoa products reduces the risk of cardiovascular disease. However, the present study demonstrates that acute cocoa ingestion decreases cardiac baroreflex sensitivity (CBRS) in a dose-dependent manner in healthy older adults. Because low CBRS may be associated with adverse cardiovascular events, the effects of cocoa on reducing CBRS warrant attention, particularly in individuals with compromised cardiovascular regulation.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R442-R449"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484317","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":"Diet-induced cardiac dysfunction and impaired cognitive performance in Beagles.","authors":"Elise Bokshowan, Adam M S Luchkanych, Matheus de O Costa, T Dylan Olver, Lynn P Weber","doi":"10.1152/ajpregu.00238.2025","DOIUrl":"10.1152/ajpregu.00238.2025","url":null,"abstract":"<p><p>Diet-induced dilated cardiomyopathy (DCM) in dogs has been linked to grain-free, pea-containing diets, possibly due to increased oligosaccharides. Since cross-sectional human studies indicate that heart failure is associated with decreased cerebral blood flow and cognitive decline, we explored whether a similar association could be detected in dogs. This study tested whether diet-induced cardiac impairment coincides with a lower index of cerebral blood flow and cognitive decline in dogs. Eight adult Beagles were fed four diets for 5 wk each. A commercial dental diet was fed prestudy as a husbandry diet, followed by three test diets fed in a randomized crossover design: a grain-based diet formulated with rice flour (GB), a grain-based diet with rice flour and 1% of the oligosaccharide raffinose (GB-O), and a grain-free diet containing pea flour (GF). Cardiac function and brain blood flow were assessed using ultrasound, and cognitive function using a sand maze test. Ejection fraction was lower, and left ventricular end-systolic volume was greater in dogs fed the GF and husbandry diets compared to the GB and GB-O diets. End-diastolic velocity and conductance index were greater in basilar cerebral arteries, whereas resistive index was lower in dogs fed GF and husbandry diets. Sand maze retrieval times were slower for GF and husbandry diet-fed dogs compared with the GB-O diet. Thus, reduced ejection fraction was associated with lower cerebral vascular tone and cognitive function in dogs fed GF and husbandry diets. This study is suggestive of a novel link between diet, cardiac function, and cognition in dogs.<b>NEW & NOTEWORTHY</b> This study is the first to investigate the heart-brain connection in dogs, revealing parallel emergence of subclinical cardiac dysfunction and reduced cognitive performance under certain dietary conditions in Beagles. Additionally, transcranial Doppler ultrasound identified a reduction in the index of cerebrovascular tone, potentially reflecting a compensatory response to early cardiac dysfunction. These findings provide a basis for further exploration of how diet, cardiac function and cognition may influence one another in dogs.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R416-R427"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430260","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 stage of mechanisms of pathological cerebral blood flow reduction due to severe central hypovolemia: a study using maximal lower body negative pressure.","authors":"Ai Hirasawa, Takuro Washio, Tomoya Suda, Kazukuni Hirabuki, Marina Fukuie, Shotaro Saito, Noritaka Hata, Takeaki Matsuda, Jun Sugawara, Shigehiko Ogoh, Shigeki Shibata","doi":"10.1152/ajpregu.00181.2025","DOIUrl":"10.1152/ajpregu.00181.2025","url":null,"abstract":"<p><p>We hypothesize that excessive central blood flow reduction leads to failure in the mechanism that appropriately distributes cerebral blood flow (CBF), preceding the pathological drop in blood pressure. This study aims to evaluate changes in CBF and cerebrovascular resistance in response to reduced cardiac output (CO) during severe central hypovolemia and elucidate the breakdown of cerebral circulation maintenance mechanisms before presyncope. Nine healthy men underwent maximal lower body negative pressure (LBNP), with ultrasound measurements of the internal carotid artery (ICA) and vertebral artery (VA) blood flow, and CO. Hemodynamic changes, including total peripheral resistance (TPR) and fractional CBF (CBF/CO), were assessed. CO decreased from LBNP25%, while ICA and VA blood flow were preserved up to LBNP50% but declined from LBNP75%. CBF/CO increased until LBNP75%, then plateaued or slightly decreased. TPR increased from LBNP50% to LBNP75%, then plateaued. Both ICA-CVRi and VA-CVRi increased with higher LBNP loads. ICA-CVRi showed significant elevations at LBNP75% and LBNPpremax, whereas VA-CVRi reached a significantly higher value at LBNPpremax. The decrease in ICA and VA blood flow was smaller than that in CO. The maintenance of blood flow at higher LBNP loads is likely due to peripheral vascular constriction, but this compensatory mechanism failed at LBNP75%, just before presyncope.<b>NEW & NOTEWORTHY</b> This study examined cerebral blood flow (CBF) responses to reduced cardiac output (CO) during severe central hypovolemia. The CBF/CO ratio increased but plateaued at 75% lower body negative pressure (LBNP). Decreases in internal carotid and vertebral artery blood flow were smaller than the CO reduction. CBF was maintained at high LBNP levels, likely via peripheral vasoconstriction. However, this compensatory mechanism failed at 75% LBNP, immediately before presyncope, indicating a breakdown in cerebral circulatory regulation.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R301-R309"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146091658","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":"Postocclusive muscle reoxygenation kinetics and nitric oxide bioavailability following 10-day bed rest.","authors":"Giorgio Manferdelli, Letizia Rasica, Andrea M Pilotto, Lucrezia Zuccarelli, Giovanni Baldassarre, Mia C Burleigh, Chris Easton, Mauro Marzorati, Boštjan Šimunič, Rado Pišot, Marco V Narici, Bruno Grassi, Simone Porcelli","doi":"10.1152/ajpregu.00093.2025","DOIUrl":"10.1152/ajpregu.00093.2025","url":null,"abstract":"<p><p>Bed rest (BR) studies have demonstrated the detrimental effects of microgravity and physical inactivity on cardiovascular function, including the negative consequences on microvascular function and O₂ extraction. However, whether a short period of BR affects microvascular responsiveness and its molecular mediator, nitric oxide (NO), remain unclear. Nine male volunteers (23 ± 5 yr) completed 10-day horizontal BR. Microvascular postocclusive reactive hyperemia in the vastus lateralis (VL) and rectus femoris (RF) muscles were assessed by near-infrared spectroscopy during a vascular occlusion test. We calculated the rate of muscle deoxygenation during the first minute of occlusion (<i>slope 1</i>) and the half-time of the reperfusion kinetics ([Formula: see text]) during the 30 s postischemia. The inverse of [Formula: see text], <i>K</i> (velocity constant) was \"normalized\" for the intensity of the ischemic/hypoxic stimulus, as estimated by [Formula: see text], the highest [Formula: see text] value at the end of ischemia. Plasma nitrite ([Formula: see text]) and nitrate ([Formula: see text]) concentrations (NO bioavailability indexes) were determined by chemiluminescence. <i>Slope 1</i> and [Formula: see text] were slower after BR in both VL (0.08 ± 0.03 vs. 0.06 ± 0.02 µM·s^-1, <i>P</i> = 0.016; and 12 ± 3 vs. 17 ± 2 s, <i>P</i> = 0.002) and RF (0.07 ± 0.02 vs. 0.05 ± 0.02 µM·s^-1, <i>P</i> = 0.008; and 12 ± 3 vs. 18 ± 4 s, <i>P</i> < 0.001). No differences were detected in <i>K</i>/[Formula: see text] after BR (VL: 0.15 ± 0.04 vs. 0.17 ± 0.03 µM·min^-1, <i>P</i> = 0.166; RF: 0.20 ± 0.06 vs. 0.21 ± 0.05 µM·min^-1, <i>P</i> = 0.220). Plasma [Formula: see text] concentration was reduced after BR (87 ± 37 vs. 67 ± 48 nM, <i>P</i> = 0.011), but not plasma [Formula: see text] concentration (43 ± 24 vs. 29 ± 11 µM, <i>P</i> = 0.130). In conclusion, 10-day horizontal BR does not impair microvascular postocclusive reactive hyperemia parameters, despite decreasing plasma [Formula: see text] concentration.<b>NEW & NOTEWORTHY</b> Short-term (10 days) horizontal bed rest does not affect skeletal muscle microvascular function when assessed via near-infrared spectroscopy and postocclusion reactive hyperemia. However, both skeletal muscle resting oxygen consumption and nitric oxide bioavailability decrease following 10-days bed rest. Future studies should investigate the time course of changes in skeletal muscle microvascular function following longer period of microgravity/inactivity.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R347-R355"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218512","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":"Impacts of prenatal resiquimod exposure during late gestation on rat offspring development and behavior.","authors":"Monique Martinez, Stuart A Tobet, Taben M Hale","doi":"10.1152/ajpregu.00287.2025","DOIUrl":"10.1152/ajpregu.00287.2025","url":null,"abstract":"<p><p>Maternal stress during pregnancy causes changes in circulating glucocorticoids and inflammatory cytokines that can alter fetal development. Prior studies have shown that prenatal dexamethasone impacts fetal brain development, increases anxiety-like behavior, and dysregulates neuroendocrine and autonomic function in adult rat offspring. Resiquimod (RQ) activates toll-like receptor 7, causing immune activation. The current study investigated the impact of RQ-induced maternal immune activation during late gestation on rat offspring development and behavior. Pregnant dams were weighed daily. On <i>gestation day 18</i>, dams were injected with vehicle (phosphate-buffered saline) or RQ (1 mg/kg). Early maternal caregiving behavior was assessed. Offspring were tracked by day of vaginal opening and weekly body weights as maturation milestones. Open field tests were conducted in separate cohorts of male and female offspring before (3-4 wk old) and after (8-10 wk old) the onset of puberty to assess anxiety-like behavior. RQ-injected pregnant dams had attenuated weight gain. However, this exposure did not affect early maternal caregiving behavior or litter metrics. Female offspring of RQ-injected dams experienced a significant delay (∼1 day) in vaginal opening, suggesting delayed pubertal onset. There were no effects of prenatal RQ on offspring weights or open field behaviors before puberty. Adult male and female offspring of RQ-injected dams had attenuated weight gain and increased anxiety-like behavior. The emergence of behavioral changes in adulthood suggests that late-gestation prenatal RQ impacts fetal brain development, as revealed by gonadal hormones and metabolic maturation. These changes highlight puberty as critical for exposing the effects of maternal immune activation.<b>NEW & NOTEWORTHY</b> Maternal stress during pregnancy affects offspring development and health. Data from the project show that maternal immune stress induced by resiquimod during late gestation in rats attenuated maternal weight gain and delayed female pubertal onset, increased anxiety-like behavior after puberty, and lessened weight gain over time in offspring. These results highlight puberty as critical for exposing the effects of prenatal stress and underscore the importance of tracking outcomes across development.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R310-R316"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13046330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218482","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":"The impact of muscle inactivity and exercise training on histidine-dipeptide homeostasis in rat skeletal muscle.","authors":"Amanda Romualdo Santana, Bianca Scigliano Vargas, Luiz Roberto Grassmann Bechara, Andressa Formalioni, Gabriella Berwig Möller, Maria Rita de Camargo Rodrigues, Wagner Ribeiro Pereira, Beatriz Cristina da Silva, Karoline Dos Prazeres Silva, Diego Pulzatto Cury, Hamilton Roschel, Anselmo Sigari Moriscot, Julio C B Ferreira, Marisa Helena Gennari de Medeiros, Livia de Souza Gonçalves, Guilherme Giannini Artioli","doi":"10.1152/ajpregu.00105.2025","DOIUrl":"10.1152/ajpregu.00105.2025","url":null,"abstract":"<p><p>Evidence suggests that muscle activity can affect muscle carnosine, but the results are mixed. To address this question, we investigated muscle carnosine under two extremes of the muscle activity-inactivity spectrum. Forty-five male Wistar rats were divided into three groups: immobilization (<i>n</i> = 16), SHAM control (<i>n</i> = 14), and immobilization + exercise (<i>n</i> = 15). In the immobilized groups, one side was submitted to a sciatic nerve sectioning surgery, with the opposite side being submitted to a SHAM control surgery, creating four experimental conditions: denervated (DEN), SHAM active control (SHAM), denervated + exercise (DEN + Ex), and SHAM + exercise (SHAM + Ex). The immobilization period was 12 wk, and the swimming training period was 10 wk (4 times per week, up to 30 min per session). The <i>tibialis anterior</i> (TA) and soleus muscles from both sides were assessed for carnosine and anserine contents, total histidine-dipeptides (HCDs), cross-sectional fiber area (CSA), and fiber type distribution. Contractile function was determined ex vivo in the <i>extensor digitorum longus</i>, and the expression of the <i>Carns1</i>, <i>Cndp2</i>, and <i>TauT</i> genes was determined with real-time polymerase chain reaction in TA. Physical inactivity drastically reduced muscle mass, contractile function, and fiber CSA. Long-term postdenervation muscle paralysis reduced muscle carnosine and anserine content, which was not dependent on diet, age, sex, or fiber type. This demonstrates that muscle inactivity is a strong modulator of muscle HCD content, at least under extreme conditions. Gene expression was not significantly altered in any of the experimental conditions. Exercise training, on the other hand, did not affect muscle HCDs and may be a less potent regulator of muscle HCD content.<b>NEW & NOTEWORTHY</b> This study demonstrated that an extreme model of muscle inactivity in rats (i.e., 12 wk of hindlimb paralysis following denervation) resulted in a substantial decline in muscle carnosine and anserine, which occurred irrespective of fiber type shift. Conversely, exercise training had no effect on histidine-dipeptide content. These findings, along with previously published studies, reinforce the notion that muscle inactivity is an important modulator of histidine-dipeptide homeostasis in skeletal muscle.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R368-R378"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275719","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":"Effect of heat acclimation training frequency on the physiological adaptations of Thoroughbred horses.","authors":"Yusaku Ebisuda, Yu Kitaoka, Yuji Takahashi, Fumi Sugiyama, Toshinobu Yoshida, Kazutaka Mukai","doi":"10.1152/ajpregu.00284.2025","DOIUrl":"10.1152/ajpregu.00284.2025","url":null,"abstract":"<p><p>Heat acclimation enhances thermoregulation and cardiovascular function. Although daily training protocols are typically recommended for humans, optimal training protocols for Thoroughbred horses remain unclear. Here, we compared the effects of two heat acclimation protocols, consecutive and intermittent, in Thoroughbred horses. In a randomized crossover study, eight trained Thoroughbred horses completed either a consecutive (CONS: 9 consecutive days) or an intermittent (INT: 3 days/wk for 3 wk) heat acclimation protocol, comprising 30 min of exercise in hot conditions (WBGT 30°C). Incremental exercise tests were performed before and after heat acclimation. Pulmonary artery temperature (T_PA), cardiovascular function, blood gases, plasma lactate, and HSP expression in skeletal muscle were assessed. Both protocols decreased resting T_PA (CONS, -0.24°C; INT, -0.25°C), increased the velocity at which T_PA reached 40°C (CONS, +14.4%; INT, +4.2%), and improved time to exhaustion (CONS +5.7%; INT +11.6%). Increased markers of aerobic performance were also observed, including V̇o_2max (CONS, +7.5%; INT, +3.4%), the speed eliciting V̇o_2max (CONS, +6.5%; INT, +10.4%), and HRmax (CONS, +10.6%; INT, +7.6%). The CONS group showed greater improvement of maximal stroke volume (CONS, +11.8%; INT, +3.9%) and body weight reduction (CONS, -1.8%; INT, -0.6%), whereas the INT group showed higher upregulation of HSP70 expression (CONS, +9.9%; INT, +21.5%). Both protocols elicited beneficial physiological adaptation, with differences in cardiovascular responses, body weight reduction, and HSP70 expression. These findings shed light on equine heat acclimation and may help to optimize training strategies for racehorses competing under heat stress.<b>NEW & NOTEWORTHY</b> This is the first study comparing consecutive and intermittent heat acclimation protocols in thoroughbred horses. Both protocols improved thermoregulation, aerobic capacity, and cardiovascular function, with several differences; consecutive training elicited higher cardiovascular adaptation and body weight loss, whereas intermittent training promoted higher HSP70 expression. These findings suggest that heat exposure frequency induces partially distinct physiological adaptations, providing new evidence to guide conditioning strategies for race horses in hot environments.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R428-R438"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472454","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":"Brain oxygen responses induced by arousing stimuli and fentanyl: generalized or structure-specific?","authors":"Feonil G Limiac, Ali Arce, Eugene A Kiyatkin","doi":"10.1152/ajpregu.00332.2025","DOIUrl":"10.1152/ajpregu.00332.2025","url":null,"abstract":"<p><p>Brain oxygen levels fluctuate with changes in neural activity and systemic physiology, yet it remains unclear whether oxygen responses to salient stimuli are structure-specific or reflect generalized brain activation. Using oxygen sensors coupled with high-speed amperometry in freely moving rats, we compared oxygen dynamics in three structures with markedly different neuronal firing properties: nucleus accumbens, medial thalamus, and substantia nigra pars reticulata, along with simultaneous measurements in the subcutaneous space. Natural arousing stimuli produced rapid oxygen increases in all brain sites coupled with robust subcutaneous oxygen decreases, though there are minor differences in magnitude. In contrast, intravenous fentanyl (30 µg/kg) induced uniform hypoxic responses in all brain sites, consisting of a rapid and strong decrease followed by a weaker posthypoxic rebound, with low between-site variability. These findings show that physiological oxygen increases during arousal are largely generalized and likely dominated by systemic mechanisms such as peripheral vasoconstriction, cerebral vasodilation, and global increases in cerebral blood flow, whereas fentanyl-induced hypoxia reflects purely systemic effects induced by respiratory depression. Overall, these results indicate that brain oxygen dynamics are shaped predominantly by systemic physiology rather than local neuronal firing properties, highlighting important constraints on interpreting oxygen-based signals as markers of neuronal activity.<b>NEW & NOTEWORTHY</b> Brain oxygenation is often used to infer local neuronal activity, but the extent to which it reflects local versus brain-wide processes remains unclear. By comparing oxygen dynamics across several brain regions and peripheral tissue in awake rats, we found that arousing stimuli evoke similar brain oxygenation increases dominated by systemic physiological mechanisms. In contrast, fentanyl induces uniform hypoxia reflecting respiratory depression. These findings show brain oxygenation largely reflects systemic states rather than local neuronal firing.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R408-R415"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13088251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147375851","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":"Reply to Liu and Steinback.","authors":"Massimo Nardone, Philip J Millar","doi":"10.1152/ajpregu.00048.2026","DOIUrl":"https://doi.org/10.1152/ajpregu.00048.2026","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":"330 4","pages":"R439-R441"},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626801","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}