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

{"title":"Stretching our understanding: is the human mechanoreflex more than a small, transient contributor to sympathetic regulation?","authors":"Seth W Holwerda","doi":"10.1152/ajpregu.00151.2026","DOIUrl":"10.1152/ajpregu.00151.2026","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R387-R389"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688335","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":"Relationships between plasma volume, fluid regulatory hormones, and maximal oxygen uptake following fixed-workload heat acclimation in men and women.","authors":"Andrew M Greenfield, Shaun C Brazelton, Billie K Alba, Phillip O Bodurtha, K Riley Connor, Nisha Charkoudian, Benjamin A Fry, Samantha J Goldenstein, Thomas A Mayer, David H Gonzalez-Rojas, Benjamin J Ryan, Afton D Seeley, MariaLena A Shaw, Roy M Salgado, Gabrielle E W Giersch","doi":"10.1152/ajpregu.00274.2025","DOIUrl":"10.1152/ajpregu.00274.2025","url":null,"abstract":"<p><p>Plasma volume (PV) expansion may support various adaptations associated with heat acclimation (HA), including a potential increase in temperate maximal oxygen uptake (V̇o_2max). The PV response to HA is highly variable, and mechanisms that contribute to this variability are poorly understood, including the potential influence of sex. Twenty-six volunteers (11 M; 15 F) underwent a 10-day HA program that consisted of 120 min of fixed-workload treadmill exercise at 40°C and 40% relative humidity (RH). Temperate (∼20°C) V̇o_2max and PV (carbon monoxide rebreathing) were measured before and after HA. Serum aldosterone, estradiol, and progesterone, as well as plasma copeptin, were measured on the first and last day of HA. HA was successfully induced, as evidenced by reductions in body core temperature, heart rate, and increased sweating rate during exercise in the heat. PV (Pre: 3,280 ± 552 mL, Post: 3,380 ± 685 mL; <i>P</i> = 0.096) and V̇o_2max (3.06 ± 0.82 L/min, 3.09 ± 0.77 L/min; <i>P</i> = 0.453) were unchanged with HA at the cohort level, and sex did not modify responses to HA (interaction effects: <i>P</i> > 0.05). ΔAldosterone was correlated with ΔPV (<i>P</i> = 0.047, <i>r</i> = 0.393, <i>r</i>² = 0.155) and Δprogesterone with ΔPV in women (<i>P</i> = 0.039, <i>r</i> = 0.537, <i>r</i>² = 0.289). In our young, healthy cohort of men and women, PV and V̇o_2max were unchanged after fixed-workload HA, and the overall adaptive response did not differ based on sex. The PV response was highly variable across individuals such that increases in PV were not observed in most individuals. Interindividual variability in circulating progesterone may contribute to some of the response in women.<b>NEW & NOTEWORTHY</b> We provide the first direct assessment of the plasma volume (PV) and volume regulatory responses to a practical, fixed-workload heat acclimation (HA) protocol in men and women. Maximal oxygen uptake was not influenced by HA, sex, or individual changes in PV. In women, progesterone was correlated with PV changes following HA.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R435-R445"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The growth of developing oocytes and hypothalamus-pituitary-ovary functions in goldfish under absolute food deprivation.","authors":"Vahidehalsadat Mirjalili, Negar Kazori, Sayyed Mohammad Hadi Alavi, Mahdi Golshan, Azadeh Hatef, Magdalena Socha, Sylvain Milla, Suraj Unniappan, Otomar Linhart","doi":"10.1152/ajpregu.00034.2026","DOIUrl":"10.1152/ajpregu.00034.2026","url":null,"abstract":"<p><p>Food deprivation (FD) seriously affects puberty onset and oogenesis in female fishes. It has been suggested that meal-responsive peptides interact with hypothalamus-pituitary-ovary (HPO) functions; however, current knowledge regarding the integration of metabolism with reproduction remains inconclusive. In the present study, we investigated the effects of 7 days absolute FD on the reproductive system of adult female goldfish (<i>Carassius auratus</i>). The number of nonvitellogenic oocytes was higher in the food-deprived goldfish than in fed goldfish, whereas the number of vitellogenic oocytes was lower (<i>P</i> < 0.05). However, FD had no effects on gonadosomatic index, ovarian reserve, oocyte diameter at different growth stages, and circulating levels of 17-β estradiol and testosterone. Analysis of hypothalamus-pituitary hormones revealed no significant changes in <i>kiss1</i>, <i>gprg54</i>, or <i>gnrh3</i> mRNA levels in the food-deprived goldfish, whereas circulating luteinizing hormone (Lh) level was increased (<i>P</i> < 0.05). These findings suggest that the FD-induced increase in Lh level was not mediated by activation of the Kiss-Gnrh system. Ovarian transcript of ghrelin <i>O</i>-acyltransferase (<i>goat</i>) mRNA, which encodes the enzyme that octanoylates ghrelin, was also increased in the food-deprived goldfish, along with decreases in hepatosomatic and viscerosomatic indices. Taken together, our results show that FD inhibits the growth of developing oocytes along with enhancement of posttranslational modification of ghrelin in the ovary. This study provides novel insight into the integration of metabolic signals with HPO hormones in the female fish.<b>NEW & NOTEWORTHY</b> Food deprivation (FD) seriously interferes with the female reproductive system. Our findings show FD-inhibited growth of developing oocytes along with decrease in hepatosomatic index, and increase in the ovarian <i>goat</i> mRNA encoding the enzyme for the acyl-modification of ghrelin. Sex steroid levels and <i>kiss1</i>, <i>gpr54</i>, and <i>gnrh3</i> mRNAs remained unchanged, whereas circulating Lh was increased under FD. This study provides novel information to better elucidate integrative physiology of hypothalamus-pituitary-ovary with oocyte growth under FD.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R324-R335"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468411","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":"Time matters: BMAL1 and cardiovascular-kidney-metabolic health.","authors":"Lance Dylan Reynolds, Zhengrong Guan, Jennifer S Pollock","doi":"10.1152/ajpregu.00041.2026","DOIUrl":"10.1152/ajpregu.00041.2026","url":null,"abstract":"<p><p>Modern lifestyles increasingly promote unhealthy eating behaviors, contributing to the global rise in cardiovascular-kidney-metabolic diseases (CKMD). Circadian rhythms, anticipatory responses that coordinate biological processes with the 24-h rotation of the earth, are tightly linked to feeding behavior and nutrient metabolism, which are crucial for cardiovascular-kidney-metabolic homeostasis. At the molecular level, core circadian \"clock genes\" take part in a highly-conserved, regulatory feedback loop that optimizes metabolic processes for the anticipated time of food intake. Among the molecular components of the circadian clock, the transcription factor brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (BMAL1) plays a central role in coordinating metabolic functions. Notably, BMAL1 and feeding behavior are at the intersection of circadian biology and metabolism, regulating each other. In this review, we summarize recent insights in metabolic physiology from global and tissue-specific <i>Bmal1</i> knockout animal models, highlighting how BMAL1 influences CKMD consequences in response to dietary composition and feeding schedules and whether sex is a determinant in these outcomes. We also discuss the potential of molecular clock-targeted therapies for CKMD. Maintaining circadian integrity is central to mitigating CKMD; thus, modulating clock-regulated pathways may offer novel therapeutic strategies.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R469-R491"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148672966","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":"Influence of lowered muscle temperature upon postexercise hemodynamics.","authors":"Brianna Rowe, Phillip Tracy, John Frerichs, Nathan B Morris, James Pearson","doi":"10.1152/ajpregu.00107.2026","DOIUrl":"10.1152/ajpregu.00107.2026","url":null,"abstract":"<p><p>Our aim was to test the hypothesis that independently lowering muscle tissue temperature would attenuate postexercise increases in leg vascular conductance and decreases in arterial blood pressure. Eleven participants (4 females; age, 27 ± 6 yr; height, 176 ± 10 cm; weight, 72.8 ± 11.3 kg; and V̇o_2max 39.34 ± 7.69 mLO₂·kg·min) completed three trials wherein they donned a water-perfused suit and exercised for 60-min at 60% V̇o_2max followed by 60-min supine recovery. Different water-circulation protocols were used to either maintain normal skin and muscle temperatures throughout recovery (normothermic), lower skin and muscle temperatures during recovery (cold), or lower muscle temperature but rewarm the skin temperature back to normal during recovery (rewarming). Internal (Tcore), skin (Tskin), and muscle temperatures (Tmuscle), mean arterial pressure, leg and cutaneous vascular conductance's were measured. Tcore was not different between trials (<i>P</i> > 0.05). Throughout the final 15 min of recovery, Tmuscle was lower (60 min: 35.94 ± 0.83°C vs. 36.74 ± 0.27°C, <i>P</i> < 0.05), but Tskin was not different (60 min: 33.8 ± 0.5°C vs. 33.9 ± 0.5°C, <i>P</i> > 0.05) in the rewarming relative to the normothermic trial. However, mean arterial pressure, leg vascular conductance, and cutaneous vascular conductance were not different between normothermic and rewarming trials (all <i>P</i> > 0.05). The findings suggest that independently lowering muscle tissue temperature after exercise does not alter whole leg vascular conductance or decreases in arterial blood pressure.<b>NEW & NOTEWORTHY</b> Our aim was to independently examine the influence of lowered muscle temperature upon leg vascular conductance and arterial blood pressure following exercise in cold or thermoneutral environments when skin and core temperatures and cutaneous vascular conductance were similar. These findings indicate that independent reductions in muscle temperature following exercise do not alter whole leg vascular conductance or postexercise arterial blood pressure when skin temperature and cutaneous vascular conductance are normal.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R336-R346"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468364","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":"Sympathetic action potential synchronicity and blood pressure regulation in healthy young adults.","authors":"Nathaniel J Iannarelli, Julia E Spafford, Cameron M Lynn, Stephen S Cheung, Deborah D O'Leary, J Kevin Shoemaker, Stephen A Klassen","doi":"10.1152/ajpregu.00082.2026","DOIUrl":"10.1152/ajpregu.00082.2026","url":null,"abstract":"<p><p>This study investigated sympathetic neural blood pressure regulation in humans by quantifying synchronous and asynchronous action potential (AP) discharge. Muscle sympathetic AP discharge was measured (microneurography; continuous wavelet transform) in 21 healthy young adults. Baroreflex functions (central baroreflex component) and diastolic blood pressure (DBP) transduction (peripheral baroreflex component) were quantified for synchronous and asynchronous AP discharge. Analyses were stratified by falling and rising blood pressures to examine hysteresis. Medium-sized synchronous APs exhibited the greatest discharge frequencies (<i>P</i> < 0.001) and baroreflex threshold gains (<i>P</i> < 0.001). Asynchronous AP discharge exhibited weak baroreflex regulation (<i>P</i> = 0.999). Central baroreflex regulation of medium-sized synchronous APs exhibited hysteresis. Medium-sized synchronous APs expressed stronger baroreflex threshold gains (sympathetic AP cluster 3: DBP Fall slope: -5.48 ± 3.07%/mmHg, DBP Rise slope: -4.71 ± 2.91%/mmHg; <i>P</i> < 0.001) and greater discharge frequencies (sympathetic AP cluster 3: DBP Fall: 0.29 ± 0.15 Hz, DBP Rise: 0.25 ± 0.13 Hz; <i>P</i> < 0.001) during falling compared with rising blood pressures. The peripheral baroreflex component exhibited hysteresis. Transduction responses to synchronous AP discharge were larger during rising compared with falling blood pressures (DBP Fall peak: 2.67 ± 1.02 mmHg, DBP Rise peak: 3.14 ± 1.29 mmHg; <i>P</i> = 0.009). Asynchronous AP discharge was associated with attenuated blood pressure reductions compared with cardiac cycles with no AP activity, and more so during rising compared with falling blood pressures (DBP Fall nadir: -2.17 ± 1.09 mmHg, DBP Rise nadir: -1.43 ± 0.68 mmHg; <i>P</i> < 0.001). These data suggest that homeostatic blood pressure regulation is achieved via distinct subpopulations of synchronous and asynchronous APs that receive different central baroreflex and nonbaroreflex inputs. Central and peripheral baroreflex hysteresis may reflect a moment-to-moment compensatory strategy for blood pressure regulation.<b>NEW & NOTEWORTHY</b> This study found that <i>1</i>) medium-sized synchronous APs exhibit central and peripheral baroreflex hysteresis and <i>2</i>) despite negligible baroreflex regulation, asynchronous APs attenuate reductions in blood pressure during cardiac cycles with no synchronous AP activity. These findings suggest that blood pressure regulation is achieved via subpopulations of synchronous and asynchronous postganglionic neurons that receive different central baroreflex and nonbaroreflex inputs. Central and peripheral sympathetic baroreflex hysteresis may reflect a moment-to-moment compensatory strategy regulating blood pressure.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R390-R401"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668203","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":"Menopausal duration and relative skeletal muscle index predict metabolic inflexibility during walking in postmenopausal women with overweight/obesity.","authors":"Tyler H Blechschmid, Perry S Battles, Emily B Long, Timothy D Mickleborough, Andrew R Coggan, Stephen J Carter","doi":"10.1152/ajpregu.00053.2026","DOIUrl":"10.1152/ajpregu.00053.2026","url":null,"abstract":"<p><p>Menopause predisposes a diminished capacity to alter oxidative substrate during exercise-a risk factor for cardiometabolic diseases (CMDs). Since walking behavior influences CMD, identifying factors associated with substrate use during walking may inform strategies to attenuate risk. This study assessed changes in lipid (ΔFATox) and carbohydrate (ΔCHOox) oxidation during walking and identified physiological predictors. Thirty-six women [64 ± 7 yr; body mass index (BMI): 29.5 ± 4.9 kg/m²] completed a treadmill task (0.9 m/s, 0% grade) with indirect calorimetry to quantify oxygen uptake (V̇o₂) kinetics, ΔFATox, and ΔCHOox. Exercise capacity was assessed via a 6-min walk test. Body composition, including relative skeletal muscle index (RSMI), was assessed using dual-energy X-ray absorptiometry. ΔFATox was correlated with age (<i>r</i> = -0.465, <i>P</i> = 0.004), menopausal duration (<i>r_s</i> = -0.478, <i>P</i> = 0.004), BMI (<i>r_s</i> = 0.398, <i>P</i> = 0.028), RSMI (<i>r</i> = 0.531, <i>P</i> = 0.001), and excessive postexercise V̇o₂ (<i>r_s</i> = 0.430, <i>P</i> = 0.009). ΔCHOox was correlated with O₂ deficit (<i>r_s</i> = 0.500, <i>P</i> = 0.002). Menopausal duration, RSMI, and recovery V̇o₂ mean response time explained the most variance in ΔFATox (adjusted <i>r</i>² = 0.534, <i>P</i> < 0.001). Menopausal duration, visceral adipose tissue mass, and O₂ deficit explained the most variance in ΔCHOox (adjusted <i>r</i>² = 0.371, <i>P</i> < 0.001). Age and menopausal duration were associated with reduced ΔFATox during walking. Menopausal duration was the strongest exploratory predictor of metabolic inflexibility. RSMI outperformed exercise capacity and V̇o₂ uptake kinetics in predicting ΔFATox during walking.<b>NEW & NOTEWORTHY</b> Changes in metabolic inflexibility were detected during walking at intensities reflecting activities of independent living in sedentary postmenopausal women with overweight/obesity. This work provides evidence for a stronger link between menopausal duration and metabolic inflexibility during walking when compared with chronological age. Our analyses also revealed that RSMI was a key predictor ΔFATox during walking and thus identified it as a clinically relevant, modifiable target for the improvement of cardiometabolic health in future clinical trials.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R502-R509"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13592042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700558","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":"Sex differences in the progression of salt-sensitive hypertension in aged Dahl salt-sensitive rats.","authors":"Ruslan Bohovyk, Olha Kravtsova, Vladislav Levchenko, Alexander Staruschenko","doi":"10.1152/ajpregu.00084.2026","DOIUrl":"10.1152/ajpregu.00084.2026","url":null,"abstract":"<p><p>Salt-sensitive hypertension is a major cardiovascular risk factor that is exacerbated by aging. Emerging evidence suggests complex mechanistic pathways involving renal sodium handling, vascular dysfunction, and hormonal alterations that vary by sex and age. The Dahl salt-sensitive (SS) rat model provides an excellent platform for investigating age-related changes in blood pressure regulation under high-salt conditions. This study examined the development of salt-sensitive hypertension in aged Dahl SS rats (>30 wk old; both males and females), focusing on sex differences in survival and blood pressure. Female animals were further categorized by breeding status (breeder vs. nonbreeder) to evaluate the effects of reproductive history on cardiovascular outcomes. Male and female rats demonstrated similar overall survival rates (60%) during the high-salt challenge, although mortality occurred earlier in females. Males exhibited lower baseline mean arterial pressure compared with females. No significant differences were observed between breeder and nonbreeder females in survival, blood pressure, or heart rate. Circadian rhythm analysis revealed that females had a higher mesor before high-salt exposure and a shifted acrophase during the first 4 days of the diet. Urinary cystatin C increased significantly in females but not in males following high-salt exposure. Overall, aged female rats exhibited higher baseline cardiovascular parameters, including blood pressure and heart-to-body weight ratio (HBW), and greater renal stress responses (cystatin C and electrolyte excretion) than males, despite similar survival rates. These findings provide new insights into sex-specific cardiovascular and renal responses to salt loading in aging and may help explain sex-dependent differences in salt-sensitive hypertension.<b>NEW & NOTEWORTHY</b> Using aged Dahl salt-sensitive rats, this study examines how aging, sex, and reproductive history influence salt-sensitive hypertension. Reproductive history did not affect cardiovascular outcomes in aged females. Integrated survival analysis, circadian blood pressure monitoring, and renal biomarkers reveal sex-specific responses to high-salt intake, providing new insights into mechanisms contributing to salt-sensitive hypertension in aging.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R494-R501"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13330727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013142","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 age and exercise training on endothelial-mediated mechanisms of vasodilation during passive leg movement in males.","authors":"Brady E Hanson, Nicholas A Carlini, Jesse C Craig, Jay R Hydren, Angela V Bisconti, Andrew C Kithas, Katherine L Shields, Soung Hun Park, Jayson R Gifford, Catherine L Jarrett, Oh Sung Kwon, Ashley D Nelson, David E Morgan, Jacob E Jessop, Amber D Bledsoe, Gregory J Stoddard, Russell S Richardson, Ryan M Broxterman, Joel D Trinity","doi":"10.1152/ajpregu.00093.2026","DOIUrl":"10.1152/ajpregu.00093.2026","url":null,"abstract":"<p><p>Passive leg movement (PLM) offers a robust method for assessing vascular function; however, the interactions among age, endothelial-mediated vasodilatory mechanisms, and exercise training-induced PLM modulation remain poorly understood. To address these gaps, the vasodilatory responses to PLM, quantified as leg vascular conductance (LVC) dynamics, were measured in younger (<i>n</i> = 9, 25 ± 4 yr) and older males (<i>n</i> = 9, 69 ± 5 yr) before and after 8 wk of single-leg knee-extension exercise training. Femoral arterial drug infusions pharmacologically dissected the contribution of the prostaglandin (PG) and epoxyeicosatrienoic acids (EETs) pathways to the residual, nitric oxide (NO)-independent component of the PLM vasodilatory response. Interrogation of these vasodilatory pathways was assessed by PLM under three conditions: control (CON), inhibition of nitric oxide synthase (NOS) alone (<i>N</i>^G-monomethyl-l-arginine, l-NMMA), and combined inhibition of NOS, cyclooxygenase (ketorolac tromethamine, KET), and cytochrome P450 (fluconazole, FLUC) (l-NMMA + KET + FLUC). Exercise training improved the PLM vasodilatory (LVC area under the curve) response in younger (4.3 ± 1.4 to 7.1 ± 4.3 mL·mmHg^-1, <i>P</i> < 0.05) but not older (2.2 ± 1.4 to 2.4 ± 1.2 mL·mmHg^-1, <i>P</i> = 0.97) males. In younger males, both l-NMMA and l-NMMA + KET + FLUC elicited significant (both <i>P</i> < 0.05) and similar (<i>P</i> = 0.99) reductions in the PLM vasodilatory response, with no effect of exercise training (<i>P</i> = 0.90). Neither l-NMMA nor l-NMMA + KET + FLUC attenuated the PLM vasodilatory response in older males before or after exercise training (<i>P</i> = 0.68 and <i>P</i> = 0.51, respectively). Together, these results indicate 8 wk of single-leg knee-extension exercise training improves the vasodilatory response to PLM in younger, but not older males, and does not alter the contribution of NO or the combined contribution of PG and EETs to PLM-induced vasodilation.<b>NEW & NOTEWORTHY</b> This study examined the impact of age and exercise training on vasodilatory mechanisms associated with passive leg movement (PLM), including nitric oxide (NO), prostaglandins (PGs), and endothelial-derived hyperpolarizing factors (EDHFs) in younger and older adult males. Following 8 wk of single-leg knee-extension exercise training, PLM was improved in younger but not older males; however, the improvement was not associated with altered contribution from NO, PG, or EDHF, suggesting other vasodilatory mechanisms may be involved.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R376-R386"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629377","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":"Agreement among common core temperature indices in defining critical environmental limits for human thermoregulation: a secondary analysis.","authors":"Olivia K Leach, Robert D Meade, Timo van den Bogaard, Fergus K O'Connor, Hein A M Daanen, W Larry Kenney, Glen P Kenny","doi":"10.1152/ajpregu.00072.2026","DOIUrl":"10.1152/ajpregu.00072.2026","url":null,"abstract":"<p><p>Global intensification of heat extremes has heightened interest in defining critical environmental limits for human thermoregulation. These limits are commonly estimated from the inflection point in core temperature during progressive heat stress protocols. Esophageal temperature (T_es) is the criterion core temperature index, as it reflects right atrial blood temperature and responds rapidly to changes in the body's thermal state. However, measurements of rectal (T_re) and gastrointestinal temperature (T_gi) are more commonly used due to better participant tolerability. We evaluated agreement between inflection points of these core temperature indices using data from two previously published progressive heat stress protocols. Study 1 measured T_es and T_re in 11 resting young adults (3 female). Study 2 evaluated T_re and T_gi in 16 resting or cycling young adults (8 females). Ambient conditions at the identified inflection points were converted to wet-bulb temperature (T_wb) and analyzed with Bland-Altman analysis (±1.3°C T_wb acceptable agreement range). In Study 1, both the mean bias [0.3°C (95% CI: 0.0°C to 0.6°C)] and the individual limits of agreement (LOA: -0.6°C to 1.3°C) for the T_es-T_re comparison were within ±1.3°C T_wb. In Study 2, the mean bias was also within the acceptable range [0.8°C (0.5°C to 1.1°C)], whereas the limits of agreement (0.6°C to 1.7°C T_wb) exceeded this threshold. Although larger confirmatory trials are needed, these findings suggest that T_re inflection identified during a progressive humidity protocol closely aligns with that identified using T_es. T_re and T_gi demonstrated acceptable group-level agreement but caution is warranted when interpreting individual responses.<b>NEW & NOTEWORTHY</b> We assessed agreement in inflection points for esophageal (T_es), rectal (T_re), and gastrointestinal (T_gi) temperatures in young adults during progressive humidity protocols. T_es and T_re exhibited good agreement on both group (study) and individual levels. Although group-level agreement between T_gi and T_re was acceptable, individual agreement was poor. These findings indicate that all three techniques are suitable for studies of critical environmental limits, though T_es or T_re are preferred when assessing individual thresholds.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R319-R323"},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13482373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547594","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}