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

{"title":"Species-specific effects of positive end-expiratory pressure on diaphragm and chest wall geometry in mice, rats, and humans.","authors":"Wout J Claassen, Myrte Wennen, Diana Jansen, Annemijn H Jonkman, J Tim Marcus, Gustav J Strijkers, Bram F Coolen, Coen A C Ottenheijm, Leo M A Heunks","doi":"10.1152/ajpregu.00258.2025","DOIUrl":"10.1152/ajpregu.00258.2025","url":null,"abstract":"<p><p>In critically ill mechanically ventilated patients, positive end-expiratory pressure (PEEP) is applied to limit alveolar collapse. However, PEEP will also affect diaphragm geometry and function. Various animal models are used to study the effects of mechanical ventilation on the diaphragm, but chest wall mechanics may influence diaphragm responses to PEEP. We hypothesized that interspecies differences are relevant when studying the effect of PEEP on diaphragm geometry during mechanical ventilation. Specifically, the chest wall compliance, which varies among species, may be an important determinant of the effect of PEEP on diaphragm geometry and function. This is relevant in future studies into diaphragm adaptations during PEEP and particularly in genetically engineered animal models. Using magnetic resonance imaging (MRI), we studied the effect of PEEP on diaphragm surface and thorax geometry in ventilated mice, rats, and healthy volunteers. PEEP reduced diaphragm surface in mice, rats, and humans, but the effect was smaller in mice compared with rats. This difference was not attributable to disparities in lung compliance or chest wall compliance. Compared with healthy volunteers, rats showed a larger decrease in diaphragm surface due to greater caudal displacement, whereas mice showed a similar decrease in diaphragm surface, but with more thoracic widening. These findings indicate that the effect of PEEP on diaphragm geometry is influenced by chest wall movement and varies across species. These findings are critical for interpreting diaphragm adaptations to mechanical ventilation in both animal models and patients.<b>NEW & NOTEWORTHY</b> Positive end-expiratory pressure, a parameter used to control end-expiratory lung volume in mechanical ventilation, has a smaller effect on diaphragm surface area in mice compared with rats. Compared with healthy volunteers, rats have a larger relative decrease in diaphragm surface area due to more caudal displacement, whereas mice have a similar decrease in diaphragm surface area, but have more widening of the thorax. Interspecies differences have to be taken into account in future (animal) research on the effects of mechanical ventilation on the diaphragm or interaction between lungs, chest wall, and diaphragm.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R571-R581"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13184903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687657","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":"Effects of sex and menstrual cycle phase on postexercise appetite regulation.","authors":"Jessica A L Tucker, Seth F McCarthy, Derek P D Bornath, Jordyn M Frayne, David A Claeys, Joshua J Aube, Tamara R Cohen, Philip J Medeiros, Tom J Hazell","doi":"10.1152/ajpregu.00328.2025","DOIUrl":"10.1152/ajpregu.00328.2025","url":null,"abstract":"<p><p>Moderate-intensity exercise interventions for weight loss are less effective in females, suggesting biological sex and fluctuations in menstrual cycle hormones may be involved. To date, no study has explored the postexercise appetite response between males, females in the follicular phase (FP), and females in the luteal phase (LP). To examine differences in appetite regulation in response to an acute bout of moderate-intensity continuous training (MICT) between males, females in the FP, and females in the LP, males and FP and LP females (<i>n</i> = 14 per group; <i>n</i> = 42 total) completed a single bout of MICT (30 min, 70% V̇o_2max). Acylated ghrelin, active glucagon-like peptide-1 (GLP-1), and subjective appetite perceptions were measured preexercise and 0, 30, 60, and 120 min postexercise. Energy intake was assessed for a 3-day period (day before, of, after). There were no between-group differences in acylated ghrelin (<i>P</i> = 0.388, [Formula: see text] = 0.047) or active GLP-1 (<i>P</i> = 0.413, [Formula: see text] = 0.044). Subjective appetite was lower preexercise in males compared with both females in the FP (<i>P</i> = 0.087, <i>d</i> = 0.85) and LP (<i>P</i> = 0.013, <i>d</i> = 0.65) with no other between-group differences. Absolute energy intake was greater in males compared with females in the LP only (<i>P</i> = 0.032, [Formula: see text] = 0.111), however, when analyzed relative to body mass there were no between-group differences (<i>P</i> = 0.306, [Formula: see text]). There were no differences in the response to MICT for appetite-regulating hormones, subjective appetite, or energy intake between males or females in either phase. Further work should consider exploring appetite following high-intensity exercise to thoroughly investigate whether sex differences on hormonal and subjective appetite regulation are present.<b>NEW & NOTEWORTHY</b> This study examined whether biological sex or menstrual cycle phase influences appetite regulation after moderate-intensity continuous exercise. Despite lower preexercise appetite perceptions in males, postexercise responses in appetite-regulating hormones, subjective appetite, and energy intake did not differ between males and females in either the follicular or luteal phase. Findings suggest that moderate-intensity exercise elicits similar appetite outcomes between males and females across the menstrual cycle, though using higher-intensity exercise should be considered in future research.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R673-R682"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759871","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 link between body heat accrual and cognition: future considerations for in-flight exercise.","authors":"Margaret Wydotis, Shelby Stocke, Lauren Rapp, Kaitlyn Bradley, Lance Bollinger, John F Caruso","doi":"10.1152/ajpregu.00035.2026","DOIUrl":"10.1152/ajpregu.00035.2026","url":null,"abstract":"<p><p>NASA's Human Research Program identified Roadmap gaps that acknowledge the importance of thermoregulation to preserve crewmember cognition. Although a resting core body temperature on Earth is 37°C, 2.5 mo in microgravity sees that same measure rise to 38°C. Of greater concern is an internal body temperature of ∼38.5°C may initiate cognitive decline, and an in-flight core body temperature may exceed 40°C during submaximal exercise. Such increases are anticipated to be a bigger concern on the upcoming Artemis (Moon) and Orion (Mars) campaigns, as crewmembers will experience longer periods of microgravity, yet the cognitive and operational demands placed upon them will remain high and unwavering throughout each mission. This review examines the potential impact between body heat accrual and cognition. Treatments that may abate body heat accrual's impact on cognition will be discussed. Due to the in-flight exercise's impact on body temperatures, countermeasures to address this concern are also described, as well as exercise recommendations for future long-term manned space missions.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R726-R735"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147939832","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":"High-altitude exercise performance and acute mountain sickness unchanged following cold water habituation.","authors":"Afton D Seeley, Thomas A Mayer, Billie K Alba, Phillip O Bodurtha, Karleigh E Bradbury, Shaun C Brazelton, Aaron R Caldwell, K Riley Connor, Gabrielle E W Giersch, Samantha J Goldenstein, David H Gonzalez Rojas, Benjamin A Fry, Andrew M Greenfield, Molly E Heikkinen, Kathryn G McCarthy, Benjamin J Ryan, Roy M Salgado, MariaLena A Shaw, John W Castellani","doi":"10.1152/ajpregu.00149.2025","DOIUrl":"10.1152/ajpregu.00149.2025","url":null,"abstract":"<p><p>Cross stress adaptation (CA) refers to the induction of physiological adaptation to one stimulus, such as cold water, to adaptively influence the physiological response to another novel stimulus, such as hypoxia. This study sought to determine if cold-hypoxia CA, induced by repeat cold-water immersion (CWI) and compared with a thermoneutral water (TN) control, could reduce resting and submaximal exercise physiologic strain, improve exercise performance, and decrease the incidence and severity of acute mountain sickness (AMS) symptoms during a 29 h exposure to hypobaric hypoxia (∼4,100 m). Cold ventilatory habituation was achieved, evidenced by an ∼20% reduction in peak minute ventilation (V̇e) and ∼31% reduction in 10 min average V̇e with six, 10-min 12°C water immersions. At 3 h of hypobaric hypoxia, an exercise bout at 50% peak oxygen uptake (V̇o_2peak) elicited greater ventilation (+3.8 [0.8-6.7] L·min^-1, <i>P</i> = 0.014) with no concomitant improvement of [Formula: see text] (TN: 76 ± 4 vs. CWI: 76 ± 4%, <i>P</i> > 0.05) following CWI. Exercise heart rate was also elevated following CWI compared with TN, irrespective of altitude exposure duration (+5 [1-8] beats·min^-1, <i>P</i> = 0.030). Two-mile time trial performance and AMS symptomology both were unchanged by repeated CWI compared with TN. Habituation to repeated cold-water immersion does not advantageously cross adapt those subsequently exposed to hypobaric hypoxia. Instead, CWI heightened early altitude ventilatory and cardiovascular strain during submaximal exercise.<b>NEW & NOTEWORTHY</b> Existing literature suggests cold habituation is capable of cross-adapting submaximal exercise ventilatory, cardiac, and catecholamine responses with normobaric hypoxia. No data exists investigating cold-to-altitude cross adaptation within real-world applicable conditions of hypobaric hypoxia. This investigation suggests that habituation to repeated cold-water immersion does not advantageously cross adapt those subsequently exposed to hypobaric hypoxia.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R652-R663"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760027","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":"Intracardiac neuromodulation of pacemaker rate in the adult zebrafish heart in vitro.","authors":"Keegan P D O'Shea, Zachary D Long, Frank M Smith","doi":"10.1152/ajpregu.00298.2025","DOIUrl":"10.1152/ajpregu.00298.2025","url":null,"abstract":"<p><p>Heart rate (HR) in vertebrates is determined by the discharge frequency of cardiac pacemaker cells, which are innervated by the autonomic nervous system. The portion of this system located within the heart, the intracardiac nervous system (ICNS), transmits impulses to cardiac effectors for control of cardiac output. Central autonomic neurons modulate the heart through sympathetic (acceleratory) and parasympathetic (inhibitory) axons in the vagosympathetic trunks. In the classical model of cardiac control, the balance between sympathetic and parasympathetic efferent signals determines HR. Recent evidence of spontaneous neural activity within the ICNS in isolated hearts suggests a local regulatory element in cardiac control. We examined the potential for ICNS modulation of HR in the isolated zebrafish heart, using atropine to block parasympathetic drive to the pacemaker and timolol to block sympathetic drive. Atropine (3, 10, and 30 µM) evoked tachycardia of similar magnitude at 22 and 28°C. Timolol (3, 10, and 30 µM) caused bradycardia at both temperatures, with greater proportional HR responses to all doses at the higher temperature. Our results suggest that both sympathetic and parasympathetic outputs from the ICNS influence the pacemaker, with the degree of sympathetic drive being temperature-sensitive. Intrinsic HR, obtained after dual antagonist application, was not significantly different from HR before drug application so the effects of sympathetic and parasympathetic drive on pacemaker rate appeared to be evenly balanced. We propose that the ICNS in the isolated zebrafish heart is capable of modulating HR in the absence of extracardiac autonomic inputs.<b>NEW & NOTEWORTHY</b> In this study, we show that the intracardiac nervous system, a key integrative pathway for autonomic control of the heart, can modulate pacemaker rate in the absence of extracardiac innervation in the isolated adult zebrafish heart. Pharmacological blockade of muscarinic and β-adrenergic receptors reveals opposing inhibitory and excitatory influences on heart rate, and these effects are eliminated when intracardiac nicotinic synaptic transmission is disrupted with hexamethonium.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R715-R725"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147866333","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":"B-Raf is required for normal murine cardiac development and function.","authors":"Natasha N Chattergoon, Katherina P Rees, Sara Lescher, Maho Takahashi, Philip J S Stork","doi":"10.1152/ajpregu.00063.2025","DOIUrl":"10.1152/ajpregu.00063.2025","url":null,"abstract":"<p><p>Developing cardiomyocytes grow by proliferative and hypertrophic pathways and can be mediated by the rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase kinase (MEK)/extracellular regulated kinase (ERK) [mitogen-activated protein kinase (MAPK)] pathway. Dysregulation of Raf-1 in late development causes murine myocardial hypertrophy; however, less is known about B-Raf. We hypothesized that the loss of B-Raf (conditional knockout) would lead to reduced neonatal cardiomyocyte proliferation and accelerate maturation, resulting in impaired function in adulthood. We also determined sex differences to ensure complete interrogation of the model. Murine neonatal hearts undergo a proliferative to terminal differentiation switch that is complete by 2 wk of age and thus studied hearts at four time points in that period (<i>days 1</i>, <i>3</i>, <i>8</i>, and <i>14</i>). Primary cultures of knockout (KO) hearts revealed reduced B-Raf and phosphorylated ERK1/2 by <i>postnatal day 3</i>, even when stimulated with insulin growth factor 1. Histology revealed increased cardiomyocyte volume in KO hearts by 3d and elevated markers of hypertrophy and maturation by 8d [mammalian target of rapamycin (mTOR) and SERC2A]. There were also elevated cell cycle inhibitors p21, p27, and p53, accompanied by increased cyclin levels. Heart weight to body weight ratio was greater in 8d KO compared with age-matched wild-type (WT) animals as well as other KO ages, whereas there was no difference among WT ages. The earliest signs of altered myocardium via echocardiographs were detected by 3 mo. KO mice exhibited dilated cardiomyopathy, thinned myocardial walls, and enlarged left chamber volume. Deletion of B-Raf led to adaptive remodeling of male KO hearts. This adaptation maintains cardiac function; however, future studies will interrogate changes in the face of physiological stress.<b>NEW & NOTEWORTHY</b> Raf-1 and B-Raf are upstream kinases that modulate the activation of ERK1/2. We show that conditional deletion of B-Raf is not compensated for by an increase of Raf-1. This suggests that the two Raf isoforms have distinct functions during cardiac development. In this report, we show early molecular and cellular changes that result in functional changes by adulthood. Developing murine cardiomyocytes are sensitive to loss of B-Raf, resulting in dilated cardiomyopathy in adulthood.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R590-R608"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759938","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":"Aging diminishes thymic output, reduces naive T cells, promotes memory T-cell accumulation, and impairs thymic regeneration.","authors":"Daria M Konovalova, Madison D Cooper, Shuli Huang, Danielle X Shane, Jordyn S Mulhern, Ying Ann Chiao, Sarah Y Yuan, Yonggang Ma","doi":"10.1152/ajpregu.00242.2025","DOIUrl":"10.1152/ajpregu.00242.2025","url":null,"abstract":"<p><p>Aging increases susceptibility to a wide range of diseases, partially due to alterations in T lymphocytes. This study aimed to characterize age-related changes in T-cell output, phenotype, and function under basal conditions and after myocardial infarction (MI). Compared with young mice (2-6 mo), aged mice (≥18 mo) demonstrated reduced thymic size and fewer developing thymocytes. Accordingly, circulating T-cell counts were significantly lower in aged mice than in young mice. Interestingly, the spleen and bone marrow of aged mice showed increased T-cell accumulation, primarily due to expansion of memory T cells. Similarly, older humans (≥60 yr old) exhibited reduced circulating T cells and a higher proportion of memory T cells. Under basal conditions, aged splenic T cells expressed higher mRNA levels of proinflammatory and cytotoxic factors (e.g., <i>Ifnγ</i>, <i>Tnfα</i>, <i>granzyme b</i>, and <i>perforin</i>). Moreover, aged T cells exhibited a higher frequency of PD-1⁺, TIGIT⁺, LAG-3⁺, and CTLA-4⁺ cells compared with young T cells, indicative of an exhausted phenotype. Metabolically, aged T cells showed higher basal glycolytic and mitochondrial oxidative phosphorylation. Following MI, thymic regeneration was evident in young mice by <i>day 14</i>, whereas the aged thymus remained atrophic. In addition, aged MI mice exhibited reduced naïve T cells and increased memory T cells in the spleen and bone marrow compared with young mice. In conclusion, our study reveals that aging diminishes thymocyte output and circulating T-cell pools, facilitates memory T-cell accumulation, and compromises thymic regeneration under basal conditions and post-MI.<b>NEW & NOTEWORTHY</b> This study reveals that aging causes thymic involution and reduces thymic output and circulating T cells. Interestingly, aging promotes memory T-cell accumulation in the spleen and bone marrow. Aged T cells exhibit an exhausted phenotype with increased metabolic activity. Following myocardial infarction (MI), aged mice display impaired thymic regeneration, decreased naïve T cells, and increased memory T cells. Collectively, these findings characterize age-related changes in T cells under basal conditions and after MI.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R609-R622"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13225476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759929","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 and ovarian hormone status shape baseline cardiovascular physiology in Sprague Dawley rats.","authors":"Kristen M Garcia, Becky A Hardie, Giuditta Monti, Maya Mikrut, Daniela Valdez-Jasso","doi":"10.1152/ajpregu.00040.2026","DOIUrl":"10.1152/ajpregu.00040.2026","url":null,"abstract":"<p><p>Sex is increasingly recognized as a critical biological variable in preclinical cardiovascular research, yet baseline physiological differences between male and female animals-and the experimental decisions that shape their interpretation-remain incompletely defined. Here, we establish a quantitative experimental framework by systematically characterizing growth trajectories, cardiac scaling, anesthetic sensitivity, estrous-cycle effects, and myocardial mechanics in male, ovary-intact female, and ovariectomized (OVX) female Sprague Dawley rats. Marked sex- and hormone-dependent differences in body growth rendered simultaneous age- and weight-matching impractical and led to distinct-and sometimes opposing-inferences regarding normalized cardiac mass depending on cohort standardization strategy. Baseline hemodynamics were comparable across sex and estrous stage, whereas ovarian hormone status modulated right ventricular structure and passive myocardial mechanics. Physiological fluctuations in estrogen were associated with estrogen-dependent changes in right ventricular mass, thickness, and compliance, whereas early ovariectomy produced persistent increases in myocardial stiffness independent of hemodynamic load. OVX females also exhibited heightened sensitivity to isoflurane during surgical procedures, particularly during early operative phases. Together, these findings demonstrate that sex, circulating estrogen, and timing of ovarian hormone loss shape baseline cardiovascular phenotypes. Rather than treating sex-related variability as experimental noise, this study provides practical guidance for experimental design, normalization, and interpretation in preclinical cardiovascular research.<b>NEW & NOTEWORTHY</b> Sex differences in cardiovascular physiology are often interpreted without accounting for growth-dependent scaling and cohort standardization. Here, we show that normalization strategy, estrogen status, and the timing of ovarian hormone loss interact critically to shape cardiac structure and passive myocardial mechanics in rats. Notably, early estrogen loss increases right ventricular stiffness independent of hemodynamic load, underscoring the importance of experimental design in interpreting sex-specific phenotypes.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R683-R693"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13271528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147939781","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":"Hypoxemia and hypercapnia synergistically mediate peripheral vasoconstriction, whereas hypercapnia mediates cerebral vasodilation in resting humans.","authors":"Masahiro Horiuchi, Shodai Moriyama, Takeshi Nishiyasu, Naoto Fujii","doi":"10.1152/ajpregu.00085.2026","DOIUrl":"10.1152/ajpregu.00085.2026","url":null,"abstract":"<p><p>Simultaneous hypoxemia and hypercapnia frequently occur in conditions such as obstructive sleep apnea, which may cause peripheral and cerebral vascular dysfunction. However, how hypoxemia and hypercapnia interact in regulating peripheral and cerebral vascular responses remains incompletely understood. Eleven healthy young adults (4 females) completed three resting gas-inhalation trials (5-6 min) under different arterial O₂ and CO₂ conditions: <i>1</i>) hypoxemic normocapnia (percutaneous arterial oxygen saturation ∼85%; Hypoxemia), <i>2</i>) normoxic hypercapnia (end-tidal CO₂ partial pressure ∼55 mmHg; Hypercapnia), and <i>3</i>) hypoxemic hypercapnia (Combined). Femoral artery blood flow and middle cerebral artery mean blood velocity were continuously assessed using Doppler ultrasound and transcranial Doppler ultrasonography, respectively. These values were divided by mean arterial pressure measured by finger photoplethysmography to calculate leg vascular conductance and cerebrovascular conductance index (CVCi). Total vascular conductance was calculated as cardiac output (model-flow method) divided by mean arterial pressure. Relative to before gas inhalation, leg vascular conductance remained unchanged in all trials, whereas total vascular conductance increased during Hypoxemia. CVCi increased during Hypercapnia and Combined. When comparing the summed isolated responses (Hypoxemia + Hypercapnia) with the Combined, changes from baseline (Δ values) of leg vascular conductance tended to be lower (<i>P</i> = 0.054), and total vascular conductance was lower (<i>P</i> = 0.031) in Combined. By contrast, Δ CVCi did not differ between the summed isolated vs. Combined (<i>P</i> = 1.000). We show that hypoxemia and hypercapnia interact to augment systemic vasoconstriction, whereas hypercapnia-induced cerebral vasodilation is well preserved when combined with hypoxemia.<b>NEW & NOTEWORTHY</b> Combined hypoxemia and hypercapnia, which occurs in obstructive sleep apnea, tended to produce greater reductions in leg vascular conductance and a significantly greater reduction in total vascular conductance compared with the sum of the isolated effects. Cerebral vascular conductance index increased to a similar extent during the combined compared with the summed conditions. We show that hypoxemia and hypercapnia interact to augment systemic vasoconstriction, whereas hypercapnia-induced cerebral vasodilation is maintained when combined with hypoxemia.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R631-R638"},"PeriodicalIF":2.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809334","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":"Reply to Bie.","authors":"Nathan T Romberger, Joseph M Stock, Virginia R Nuckols, Ronald K McMillan, Megan M Wenner, William B Farquhar, Roxana G Burciu","doi":"10.1152/ajpregu.00083.2026","DOIUrl":"10.1152/ajpregu.00083.2026","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":"330 5","pages":"R561-R562"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13372079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832393","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}