Journal of applied physiology最新文献

{"title":"Dynamic cerebral autoregulation in healthy males during sleep accompanied by intermittent hypoxia.","authors":"Andrew E Beaudin, Andrew J Prsa, Patrick J Hanly, Jill K Raneri, Matiram Pun, Georgios D Mitsis, Marc J Poulin","doi":"10.1152/japplphysiol.00099.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00099.2025","url":null,"abstract":"<p><p>Obstructive sleep apnea (OSA) is an independent risk factor for stroke, potentially due to intermittent hypoxia (IH) induced impairment of cerebral autoregulation. Human cerebral autoregulation during sleep is poorly characterized and whether IH exposure during sleep alters cerebral autoregulation during sleep is unknown. In a secondary, exploratory analysis of previously collected cerebral blood flow (transcranial Doppler ultrasound measurement of peak blood velocity through the middle cerebral artery; V¯P), mean arterial pressure (MAP; finger photoplethysmography) and end-tidal partial pressure of CO₂ (PETCO₂) data, dynamic cerebral autoregulation (dCA) was quantified using transfer function analysis gain, phase and coherence in healthy males (n=10; age: 26 ± 6 years; BMI: 24.5 ± 1.7 kg/m²; MAP: 87.5 ± 8.0 mmHg) during wakefulness and during non-rapid eye movement (NREM) sleep in normoxia or accompanied by IH. Compared to wakefulness V¯P variability was lower during both sleep in normoxia and sleep accompanied by IH in the very low frequency (VLF: 0.02 - 0.07 Hz) and low frequency (LF: 0.07 - 0.2 Hz) ranges (both comparisons, p≤0.02) with MAP variability being lower in the LF range (p=0.045); gain, phase, and coherence were similar between wakefulness and sleep (all comparisons, p≥0.062). dCA measures during normoxic and IH-sleep were similar (all comparisons, p≥0.09). Moreover, dCA gain and phase, and multiple and partial coherences during IH-sleep were not different between acute (<1h) and prolonged (~2h) exposure (all comparisons, p≥0.055) even though V¯P was lower following prolonged IH exposure (p=0.002). These findings indicate dCA is effective during stages 2/3 NREM sleep and is not impacted by ~2h of sleep accompanied by IH.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292273","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":"CARDIOVASCULAR AND AUTONOMIC RESPONSES IN YOUNG ADULTS DURING AND AFTER MECHANOREFLEX ACTIVATION VIA PASSIVE FOREARM STRETCHING: ARE THERE SEX DIFFERENCES?","authors":"Georgia C S Lehnen, Rosa V D Guerrero, Giovanna M R Cunha, Marcela S Araujo, Jake C Carmo, Rachel C Drew, Bruno M Silva, Gabriel S Trajano, Lauro C Vianna","doi":"10.1152/japplphysiol.00645.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00645.2025","url":null,"abstract":"<p><p>Despite evidence suggesting that passive muscle stretching may enhance vagal modulation following the maneuver, its cardiovascular effects, particularly on cardiac baroreflex sensitivity (cBRS), during and after stretching, as well as potential sex-related differences, remain unclear. This study investigated whether activation of the muscle mechanoreflex through passive forearm stretching elicits sex-specific cardiovascular responses and modulates cardiac autonomic regulation during recovery. Twenty-four healthy young adults (13 males;age:23 ± 4years) were enrolled. After 10 minutes of supine rest with the wrist in a neutral position, participants completed two experimental conditions in randomized order on separate days: control and five sets of 1-minute passive forearm stretching (15-s rest). Cardiovascular variables were continuously recorded, including beat-to-beat heart rate (ECG), finger arterial pressure (photoplethysmography), and brachial blood pressure (automated-sphygmomanometer). cBRS was assessed using the sequence method, which identified spontaneous sequences of rising (Up) and falling (Down) systolic pressure, followed by corresponding changes in RR interval. Measurements were obtained at baseline, during, immediately after, and 15-and 30-minute post-intervention for both conditions. Passive stretching elicited a significant increase in mean blood pressure, with a sex-specific difference (males:Δ9 ± 7 mmHg; females:Δ4 ± 4 mmHg; <i>P</i>=0.015). Vagal modulation increased during recovery (Δ11 ± 16 ms; <i>P</i>=0.019). cBRS Up enhanced post-stretch (Δ3 ± 1 ms·mmHg⁻¹; <i>P</i> < 0.05), while cBRS-Down showed no significant changes. Passive forearm stretching elicits a significant pressor response, which is greater in males, and promotes increases in cardiac vagal activity and cBRS-Up, with no sex differences observed during the recovery period.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292290","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":"Habitual sleep duration is associated with heightened muscle sympathetic nerve activation and blood pressure reactivity in response to the cold pressor test.","authors":"Nathaniel D M Jenkins, Natasha G Boyes, Dain W Jacob, Brian Shariffi, Samuel A Martin, Jacqueline K Limberg","doi":"10.1152/japplphysiol.00808.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00808.2025","url":null,"abstract":"<p><p>The link between short sleep duration and cardiovascular disease may be related to exaggerated neurocardiovascular reactivity. <b>Purpose:</b> We examined the association of actigraphy-measured habitual sleep duration (HSD) with muscle sympathetic nerve activity (MSNA) and blood pressure (BP) at rest and in response to a cold pressor test (CPT). <b>Methods:</b> Thirteen adults (5M/8F; 30±9 y; 26.9±5.8 kg/m², 117±13 / 76±6 mmHg) were instrumented for measurement of beat-to-beat BP, forearm vascular resistance, and MSNA at rest and during a 2-min CPT. HSD was measured using wrist actigraphy across 6-7 days. Partial correlations (r_XY·Z) described the relation between HSD with sympathetic and cardiovascular activity at rest and in response to the CPT (Δ), accounting for sex, age, and relative body fat. <b>Results:</b> The CPT induced increases in systolic (+8.1±7 mmHg; <i>p</i>=0.002), diastolic (+6.4±4; <i>p</i><0.001) and mean BP (+7.0±4; <i>p</i><0.001), as well as in MSNA burst frequency (+9.1±8 bursts/min; <i>p</i>=0.001), burst incidence (+11.5±11 bursts/100 heartbeats; <i>p</i>=0.003), and total MSNA (+1296.6±1329 total normalized burst area/min; <i>p</i>=0.004). HSD was not associated with resting MSNA or BP (all <i>p</i>>0.14). However, HSD was strongly associated with the CPT-induced changes in MSNA burst frequency (r_XY·Z=-0.69; <i>p</i>=0.028), diastolic (r_XY·Z= -0.69; <i>p</i>=0.028) and mean BP (r_XY·Z = -0.77; <i>p</i>=0.009). <b>Conclusions:</b> Whereas HSD is not strongly associated with resting sympathetic neural activity or BP, it is associated with sympathetic and BP reactivity to physiological stress. These findings support an important role for MSNA and BP reactivity in the described association of sleep duration with CVD risk.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292306","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 energy cost of cyclic muscle contractions at different initial muscle-tendon unit lengths derived from near-infrared spectroscopy.","authors":"Spencer J Skaper, Jack J Jin, Michael J Asmussen, Jared R Fletcher","doi":"10.1152/japplphysiol.00540.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00540.2025","url":null,"abstract":"<p><p>During locomotion, the plantarflexor muscle fascicles appear to operate on the ascending limb of its maximal force-length relationship, producing less force per unit activation and elevating the energy cost (EC) compared to contractions performed at optimal length (L_o). The EC of the medial gastrocnemius muscle was quantified at different initial muscle-tendon unit lengths by having participants perform 30 submaximal fixed-end contractions at an ankle joint angle associated with 0.85L_o, L_o, and 1.15L_o in a random order, cyclically targeting 50% of the maximal force at 0.85L_o. EC was quantified from near-infrared spectroscopy during blood flow occlusion and EMG quantified MG muscle activity. Mean EC was 36±24% higher at 0.85L_o (<i>p</i>=0.005) compared to L_o. Mean EC at 1.15L_o (2±27% lower) was similar to that at L_o (, <i>p</i>=0.81), despite lower forces at 0.85L_o (<i>p</i>=0.02), and similar absolute fascicle shortening (<i>p</i>=0.10), and shortening velocity (<i>p</i>=0.52). Muscle activity was ~2-fold higher at 0.85L_o (<i>p</i>=0.001). The EC per unit activation was similar across lengths (<i>p</i>=0.45), whereas the EC per unit force was significantly higher at 0.85L_o compared to L_o and 1.15L_o (<i>p</i>=0.008). Together, these results demonstrate a significant increase in the cost of cyclically producing force at short initial muscle-tendon unit lengths, due to a lower force potential at that initial muscle fascicle length which we surmise is a result of a lower crossbridge force and not a higher energetic cost of activation.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251179","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":"Age Alters Integrated Cerebrovascular and Cardiovascular Dynamic Responses to Exercise: Insights from a Systems Modeling Approach.","authors":"Sandra A Billinger, Eric D Vidoni, Keshav Motwani, Bria L Bartsch, Tyler Baldridge, Madeline Walker, Ali Shojaie","doi":"10.1152/japplphysiol.00393.2025","DOIUrl":"10.1152/japplphysiol.00393.2025","url":null,"abstract":"<p><p>Understanding the dynamic interaction between cardiovascular and cerebrovascular systems during exercise is essential to evaluate the mechanisms supporting brain perfusion. This study examined age- and sex-specific differences in cardiovascular and cerebrovascular dynamic response and used systems modeling to assess physiological coupling during moderate intensity exercise. We recruited adults to complete a single session of moderate intensity exercise on a recumbent stepper. Middle cerebral artery blood velocity (MCAv), mean arterial pressure (MAP), heart rate (HR), and end-tidal CO₂ (P_ETCO₂) were continuously recorded. In 164 participants, we analyzed the dynamic responses to exercise using mono-exponential modeling and functional data analysis. Granger causality within a subject-specific vector autoregression framework evaluated directional influence among physiological signals. Advancing age was associated with an attenuated dynamic response for MCAv, P_ETCO₂, and HR while MAP was elevated. Older adults exhibited significantly smaller MCAv amplitude and slower time constants than young and middle-aged groups. While sex did not influence overall MCAv, MAP, or HR kinetics, men had significantly higher P_ETCO₂ throughout exercise. Granger causality analysis revealed bidirectional coupling among MCAv, HR, MAP, and P_ETCO₂. Prior P_ETCO₂ levels significantly predicted MCAv while MAP had both short- and long-lag predictive effects on MCAv. MCAv also influenced subsequent changes in MAP and P_ETCO₂, indicating feedback regulation. P_ETCO₂ emerged as a dominant driver of MCAv, though systemic interactions reflect an integrated physiological network with multi-component feedback loops. This study advances understanding of cerebrovascular regulation and highlights the utility of systems modeling during exercise.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244569","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":"Quantifying Nuanced Differences in Hand Dexterity between the Dominant and Non-Dominant Hands of Healthy, Right-Handed, Young Adults.","authors":"Brian J Conway, Léon Taquet, Timothy F Boerger, Kaitlin Goetschel, Kate B Krucoff, Sergey Tarima, Brian D Schmit, Max O Krucoff","doi":"10.1152/japplphysiol.00123.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00123.2025","url":null,"abstract":"<p><p>When individuals present with hand injuries, clinicians often use the contralateral hand as an internal control. However, subtle differences in baseline dexterous abilities between the dominant and non-dominant hands are poorly understood. To address this gap, here we quantified such differences, measured as independence (individuation) and smoothness of finger movements. A cohort of 47 right-hand-dominant healthy adults (22 males, 25 females) moved each finger independently 10 times while joint angle data were tracked with a dataglove (Cyberglove III, CyberGlove Systems, San Jose, CA). Each finger's performance was compared to its counterpart on the opposite hand using Wilcoxon-signed rank tests. The right hand scored significantly higher than the left on both direct comparison and linear mixed effect modeling for thumb individuation (p<0.0001) and smoothness (p<0.0001), index finger individuation (p=0.012), and middle finger individuation (p=0.009). Differences between the hands for index and middle finger individuation scores changed depending on the individuation scoring method used. Sex-based comparisons revealed females had greater asymmetry of thumb (p=0.044) and ring finger (p=0.020) individuation scores, as well as ring finger smoothness (p=0.036) compared to males on both direct comparison and multiple linear regression. Cluster and principal component analysis were performed to detect whole-hand differences. Dominant and non-dominant hands were separated using smoothness metrics at a 74.5% sensitivity, 66% specificity, 68.6% positive predictive value, and 72.1% negative predictive value. In sum, this represents the largest study to date quantifying naturally occurring differences in hand dexterity between dominant and non-dominant hands in healthy, right-handed young adults.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244607","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":"Reduction in respiratory muscle strength following a series of preparatory and maximal static, dry breath-holds.","authors":"Colin D Hubbard, Dario Vrdoljak, Geoff B Coombs, Troy J Cross, Bryan J Taylor, Andrew T Lovering, Ivan Drvis, Željko Dujic, Nikola Foretić, Joseph W Duke","doi":"10.1152/japplphysiol.00256.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00256.2025","url":null,"abstract":"<p><p>Breath-hold diving poses significant physiological challenges to maintaining O₂ homeostasis. During a maximal breath-hold, numerous, subsequently augmenting, involuntary respiratory muscle contractions against a closed glottis (i.e. involuntary breathing movements, IBMs) may elicit respiratory muscle fatigue, especially under conditions of arterial hypoxemia. Thus, the purpose of this study was to determine whether respiratory muscle fatigue occurs following a series static breath-holds in 14 trained male divers. To do so, we measured transdiaphragmatic twitch pressure (P_DI,TW), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) before and 8 min after three preparatory breath-holds (separated by 2.5 min; average duration = 185 ± 69 s and range = 62-309 s) and three maximal breath-holds (separated by 5 min; average duration = 308 s and range = 179-733 s). We calculated a pseudo O₂ delivery as heart rate × peripheral O₂ saturation. There was a significant reduction of P_DI,TW following the breath-hold series (-8.5 ± 13.7%; range: +7 - (-37)%; p = 0.03). Similarly, we found that MIP and MEP decreased by 6.3 ± 10.6% (p = 0.04) and 8.6 ± 10.4% (p = 0.002), respectively. Using an individualized means of determining the presence of fatigue, we observed that some (~50%), but not all divers incurred respiratory muscle fatigue. Those who developed fatigue had a lower pseudo O₂ delivery during the struggle phase than those who did not (p=0.01). Our findings suggest that respiratory muscle fatigue was more common in those divers who experienced a greater severity of arterial hypoxemia during the breath-holding protocol.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225216","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":"Comparing spontaneous neurovascular and neurohemodynamic sympathetic transduction in response to hypoxia.","authors":"Adina E Draghici, J Andrew Taylor, Jason W Hamner","doi":"10.1152/japplphysiol.00243.2025","DOIUrl":"10.1152/japplphysiol.00243.2025","url":null,"abstract":"<p><p>Assessment of sympathetic transduction into its effects on the cardiovascular system is of great interest in human research. Analysis of sympathetic transduction has been divided into neurovascular and neurohemodynamic, highlighting the sympathetic effect on either regional vascular or systemic pressure responses. This study investigates whether indices of neurovascular transduction are reflected in parallel neurohemodynamic transduction during normoxia and hypoxia, with and without accounting for the confounds of prevailing tachypnea and tachycardia. In this retrospective study in 11 healthy individuals, we measured beat-by-beat blood pressure, multiunit sympathetic nerve activity (MSNA), and popliteal blood flow velocity with normoxia and isocapnic hypoxia (∼80% [Formula: see text]). Neurovascular transduction was indexed by leg vascular conductance and neurohemodynamic transduction by systemic pressure, derived from signal averaging either conductance or pressure over 10 cardiac cycles after a sympathetic burst. Responses were assessed from raw data and data corrected for ventilation and heart rate. Compared with transduction values during normoxia, sympathetic neurovascular transduction was increased (<i>P</i> = 0.001) and neurohemodynamic transduction was greater (<i>P</i> < 0.01) but delayed (<i>P</i> = 0.03) during hypoxia. When accounting for changes in respiration and cardiac interval, the two indices provided conflicting results-sympathetic neurovascular transduction was unaltered by hypoxia; on the contrary, neurohemodynamic transduction remained increased (<i>P</i> < 0.01), but there was no longer a delayed effect. Regardless, despite corrections for confounding effects of tachypnea and tachycardia, neither neurovascular nor neurohemodynamic transduction indices explained the integrated cardiovascular responses to hypoxia.<b>NEW & NOTEWORTHY</b> Spontaneous neurovascular and neurohemodynamic sympathetic transduction can provide conflicting insight into sympathetic effects on regional and systemic hemodynamics. We examined these transduction indices in response to acute hypoxia in healthy individuals, accounting for confounds of tachypnea and tachycardia. Neither transduction measure fully explained the integrated cardiovascular response. Surprisingly, we found a strong linear relation between neurohemodynamic transduction and low-frequency blood pressure variability, suggesting caution should be used when inferring sympathetic control from hemodynamic indices.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"902-908"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000595","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":"Central command: the navigator in the storm of autonomic reflexes during simulated diving.","authors":"Alvaro Reischak-Oliveira","doi":"10.1152/japplphysiol.00733.2025","DOIUrl":"10.1152/japplphysiol.00733.2025","url":null,"abstract":"","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"951-953"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145053561","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":"No altitude required: differential ventilatory and blood acid-base homeostasis between unacclimatized lowlanders and Tibetan highlanders at 1,400 m.","authors":"Nicole V Bushfield, Nicole A Johnson, Jessica A Dickenson, Benjamin W L MacKenzie, Rodion Isakovich, Anne Kalker, Janne Bouten, Nicholas D J Strzalkowski, Taylor S Harman, Pontus Holmström, Ajaya J Kunwar, Nilam Thakur, Sunil Dhungel, Nima Sherpa, Abigail W Bigham, Tom D Brutsaert, Trevor A Day","doi":"10.1152/japplphysiol.00619.2025","DOIUrl":"10.1152/japplphysiol.00619.2025","url":null,"abstract":"<p><p>Tibetan highlanders (TH) possess physiological adaptations supporting ventilation, oxygenation, and acid-base regulation with acclimatization to chronic hypobaric hypoxia. Although well-characterized at high altitude, it is unclear whether these traits are evident at low altitude, independent of environmental hypoxic stimuli. To evaluate baseline physiological differences, we compared variables related to ventilatory, blood oxygen, and acid-base balance between unacclimatized ancestral lowlanders (LL; <i>n</i> = 29) and TH (<i>n</i> = 31) residing at 1,400 m, a subthreshold altitude not expected to elicit ventilatory or renal acclimatization. Heated hand capillary blood samples were analyzed for hemoglobin ([Hb]_c), oxygen content (C_cO₂), alveolar ventilation (V̇_A), steady-state chemoreflex drive (SSCD), partial pressure of carbon dioxide (P_cCO₂), bicarbonate ([HCO₃^-]_c), and pH_c. TH demonstrated significantly higher V̇_A (4.6 ± 0.4 vs. 4.8 ± 0.3 L/min; +5.2%; <i>P</i> = 0.0101) and SSCD (11.9 ± 1.9 vs. 13.2 ± 1.9 arbitrary units; +10.3%; <i>P</i> = 0.0127) than LL, despite equivalent [Formula: see text] (<i>P</i> = 0.8882). In addition, TH exhibited lower P_cCO₂ (37.9 ± 2.8 vs. 36.0 ± 2.5 mmHg; -5%; <i>P</i> = 0.0086) and [HCO₃^-]_c (22.9 ± 1.4 vs. 21.5 ± 1.6 mmol/L; -6.1%; <i>P</i> = 0.0007) compared with LL, with no difference in pH_c (<i>P</i> = 0.256). The reduction of [HCO₃^-]_c in TH was greater than expected from passive chemical buffering alone, suggesting differential renal handling while breathing ambient air at low altitude. These findings suggest that TH maintain a distinct ventilatory and acid-base homeostatic set point at low altitude, characterized by augmented resting ventilatory drive and renal excretion of HCO₃^-. These traits, characterized at low altitude, suggest that developmental exposure to hypoxia and/or Tibetan ancestry is associated with developed or evolved physiological traits that optimize respiratory and acid-base homeostasis prior to and/or during high-altitude ascent.<b>NEW & NOTEWORTHY</b> Understanding the role of ancestry in the regulation of ventilatory and renal homeostasis is key to interpreting high-altitude acclimatization and adaptation. We compared unacclimatized lowlanders (LL) and Tibetan highlanders (TH; Sherpa) at 1,400 m. TH had significantly lower Pco₂ and [HCO₃^-], suggesting a distinct respiratory and blood acid-base set point. These results highlight intrinsic respiratory and renal integration in TH, revealing population-level physiological differences independent of hypoxic stress, likely shaped by developmental or genetic adaptation.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1064-1072"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080833","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}