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

{"title":"The effects of two days of intermittent exogenous ketosis at high altitude on baroreflex sensitivity and ventilation under hypoxic and hypercapnic conditions.","authors":"Benjamin J Narang, Domen Tominec, Myrthe Stalmans, Grégoire P Millet, Chiel Poffé, Tadej Debevec","doi":"10.1152/ajpregu.00125.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00125.2025","url":null,"abstract":"<p><p>High-altitude (HA) exposure induces an integrated physiological response to mitigate hypoxemia. Exogenous ketosis at simulated HA was previously shown to accentuate sympathetic activation, and attenuate pulse oxygen saturation (SpO₂) decreases through hyperventilation. The aim of this study was to extend these findings by investigating the effects of intermittent exogenous ketosis (IEK) across two days at terrestrial HA (3375 m) on baroreflex, heart rate variability, and hypoxic/hypercapnic ventilatory responses. 34 healthy active adults completed neutral, hypoxic, and hypercapnic (0.03 FiCO₂) exposures, each comprising six minutes of seated rest, once at sea level (SL) and once after two days at HA. Across the two days, participants intermittently ingested either ketone monoester supplements (IEK) or placebo (PLA). During each exposure, blood pressure, ventilation, SpO₂, and end-tidal CO2 pressure (P_ETCO₂) were continuously recorded, and arterialized capillary blood gas content was measured in the final 30 s. Baroreflex sensitivity and time-domain metrics of heart rate variability were reduced at HA (<i>p</i> = 0.006-0.043), but unaffected by group (<i>p</i> = 0.288-0.525). However, ventilation at HA under all three conditions was significantly higher in IEK compared to PLA (all <i>p</i> < 0.001). In hypoxia, this induced a higher SpO₂ (<i>p</i> = 0.038) and capillary O₂ pressure (<i>p</i> = 0.003). In hypercapnia, this induced a lower P_ETCO₂ and capillary CO₂ tension (both <i>p</i> < 0.001). These results extend previous findings, suggesting that IEK enhances ventilation at terrestrial HA and after two days of exposure, with this effect being independent from baroreflex sensitivity or heart rate variability changes.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607163","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":"Unlocking the Gut: Microbiome's Role in Energy Metabolism Editorial Focus on \"Reutericyclin mitigates risperidone-induced suppression of anaerobic energy expenditure\".","authors":"Neil B Blok, Nadejda Bozadjieva-Kramer","doi":"10.1152/ajpregu.00158.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00158.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599143","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 HYPEREMIC RESPONSE TO EXERCISE IS BLUNTED IN FEMALES WITH POLYCYSTIC OVARY SYNDROME.","authors":"Will Huckins, Shannon I Delage, Danielle E Berbrier, Derek Skolnik, Hana Sandra Aiko Keightley, Charlotte W Usselman","doi":"10.1152/ajpregu.00263.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00263.2024","url":null,"abstract":"<p><p>Some beneficial adaptations to exercise training appear to be blunted in females with polycystic ovary syndrome (PCOS) relative to controls. Impaired hyperemic responses to exercise may contribute to this phenomenon. Therefore, we compared the active limb hyperemic response to acute dynamic single-leg exercise to exhaustion between lean females with PCOS (n=14, age: 23±5yr, BMI: 23±2kg/m²) and age- and BMI-matched females without PCOS (CTRL; n=14). Femoral artery blood flow (FBF; duplex vascular ultrasound) and finger photoplethysmography-derived mean arterial blood pressure (MAP) were recorded at baseline and throughout graded concentric knee extensions to exhaustion (Biodex Pro 4 dynamometer). Resting FBF was not different between PCOS and CTRL (416±238 vs. 360±163 ml/min, respectively; <i>P</i>=0.43). FBF and leg vascular conductance responses to exercise were blunted in PCOS relative to CTRL (effects of group: P<i>=0.03</i> and <i>0.02</i>, respectively). Resting MAP was higher in PCOS than CTRL (91±6 vs. 86±7 mmHg; <i>P</i>=0.04), while MAP responses to exercise were not different between PCOS and CTRL overall (effect of group P=0.31). In sum, we observed blunted hyperemic responses throughout exercise in this cohort of relatively healthy females with PCOS.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599130","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":"Impact of dopamine on baroreflex-mediated sympathetic arterial pressure regulation in rats: An open-loop analysis.","authors":"Nana Hiraki, Toru Kawada, Masafumi Fukumitsu, Takuya Nishikawa, Hiroki Matsushita, Yuki Yoshida, Kei Sato, Hidetaka Morita, Masahiro Otake, Kenta Ohba, Kazunori Uemura, Joe Alexander, Keita Saku","doi":"10.1152/ajpregu.00020.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00020.2025","url":null,"abstract":"<p><p>Dopamine is commonly used to treat hemodynamic collapse, but its effect on baroreflex-mediated sympathetic arterial pressure (AP) regulation remains to be elucidated. We quantified the effects of dopamine on AP regulation using a baroreflex open-loop analysis by measuring sympathetic nerve activity (SNA) and AP in response to stepwise changes in carotid sinus pressure (CSP) before and during intravenous infusion of dopamine at 2, 10, and 20 μg·kg^-1·min^-1 in anesthetized rats (n = 8). We analyzed the CSP-SNA relationship (neural arc) and the SNA-AP relationship (peripheral arc), and constructed a baroreflex equilibrium diagram. The gain at the operating point was calculated from the product of the tangential slope of the neural arc and the slope of the peripheral arc. Compared to baseline, dopamine at 20 μg·kg^⁻¹·min^⁻¹ significantly reduced the maximum gain of the neural arc [from 1.898 ± 0.150 to 1.277 ± 0.205 %/mmHg (<i>P</i> = 0.014)]. Compared to baseline, dopamine at 10 and 20 μg·kg^⁻¹·min^⁻¹ significantly reduced the slope of the peripheral arc [from 0.806 ± 0.079 to 0.645 ± 0.091 mmHg/% (<i>P</i> = 0.031) and 0.633 ± 0.100 mmHg/% (<i>P</i> = 0.020), respectively] and the operating point gain [from 0.800 ± 0.187 to 0.462 ± 0.153 mmHg/mmHg (<i>P</i> = 0.008) and 0.345 ± 0.122 mmHg/mmHg (<i>P</i> < 0.001)], while maintaining the operating point AP. In conclusion, dopamine at 10 and 20 μg·kg^⁻¹·min^⁻¹ maintained the operating point AP but significantly reduced the operating point gain for AP regulation, potentially increasing AP variability and instability.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599129","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":"Heart failure decreases adipocyte progenitors with impaired differentiation capacity toward mature adipocytes.","authors":"Yusuke Takeda, Oto Inoue, Ayano Nomura, Daiki Hashimuko, Kosei Yamaguchi, Chiaki Goten, Shinichiro Takashima, Masayuki Takamura, Soichiro Usui","doi":"10.1152/ajpregu.00191.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00191.2024","url":null,"abstract":"<p><p>Cardiac cachexia, characterized by adipose tissue atrophy, has the most unfavorable outcome in heart failure (HF). Adipose dysfunction might worsen HF as adipose tissue has been found to have cardioprotective effects mediated through its metabolic and endocrine functions, and therefore, could serve as a novel therapy target. In the context of adipose tissue homeostasis, adipocyte progenitor cells (APCs) play critical roles in maintaining the number and function of mature adipocytes, including lipid metabolism and hormone secretion. However, the mechanism by which HF affects APCs has not been elucidated. In this study, we aimed to evaluate the number and functions of Lin^-CD24⁺ APCs in the subcutaneous adipose tissue of mice subjected to transverse aortic constriction-induced HF. This HF model greatly reduced the number of APCs and increased their apoptosis, resulting in lipodystrophy. In vitro assays revealed that HF limited APC proliferation and senescence. With respect to the mechanism of impaired APC function in HF, we identified that augmented sympathetic nerve activity partially mediated the decrease in APC counts via unilateral adipose tissue denervation (ATD). Furthermore, ATD mitigated HF-induced APC senescence. We elucidated that HF and excess sympathetic nerve activity impaired the adipogenic differentiation capacity of APCs. In conclusion, HF induced APC loss and senescence by augmenting sympathetic nerve activity. The impaired adipogenic capacity of APCs results in reduced healthy adipose tissue mass, suggesting that this phenomenon could be responsible for the worsening of HF.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551733","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":"Modeling COPD in <i>Drosophila melanogaster</i> by cigarette smoke inhalation: functional changes and alterations in the expression of COPD-relevant orthologous genes.","authors":"Periklis Marnas, Stefan Lüpold, Lydia Giannakou, Athanasios-Stefanos Giannopoulos, Chrissi Hatzoglou, Konstantinos I Gourgoulianis, Sotirios G Zarogiannis, Erasmia Rouka","doi":"10.1152/ajpregu.00056.2025","DOIUrl":"10.1152/ajpregu.00056.2025","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) ranks as the fourth leading cause of mortality worldwide. Long-term exposure to airway irritants such as smoking and air pollution is the main risk factor for developing the disease. Expanding on previous in silico findings on COPD-relevant orthologous genes between humans and <i>Drosophila melanogaster</i>, we experimentally investigated the contribution of cigarette smoke (CS) inhalation exposure to the induction of COPD-related physiological and transcriptomic modifications. Adult flies 2-4 days old were exposed to CS via inhalation for 20 min over five consecutive days. The metabolic rate, locomotor activity, body mass, total body length, and the expression of COPD-specific genes were measured and compared between the exposed and unexposed groups. CS inhalation exposure significantly increased the metabolic rate and decreased the locomotor activity, body weight, and total body length. Transcriptomic changes were more profound in females, indicating sex-specific differences in CS-induced molecular responses. Functional enrichment analyses of the differentially expressed COPD-relevant genes in females pointed toward ABC transporters, miR-313 microRNA, abnormal developmental rate, DNA repair, and cell differentiation. Our results indicate that <i>D. melanogaster</i> is a powerful model organism for studying the pathophysiological changes associated with COPD. Future work should focus on establishing tracheolar-related changes that would reflect histopathological perturbations similar to COPD patients' airways.<b>NEW & NOTEWORTHY</b> Inhalation exposure of adult <i>D. melanogaster</i> to cigarette smoke induced changes in physiological parameters and the expression of COPD-associated orthologous genes. Transcriptomic responses were more profound in females, indicating sex-specific responses to inhaled toxicants. Furthermore, enrichment analyses of the differentially expressed genes in females pointed to biomolecules associated with response to nicotine and detoxification. <i>D. melanogaster</i> thus provides a powerful model system to test the efficacy of new potential drugs for COPD treatment.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R13-R19"},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109385","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":"G tolerance and vascular sympathetic reflex responses as affected by repeated prolonged exposures to increased force field.","authors":"Ola Eiken, Michail E Keramidas, Antonis Elia, Heather M Bowes, Roger Kölegård","doi":"10.1152/ajpregu.00036.2025","DOIUrl":"10.1152/ajpregu.00036.2025","url":null,"abstract":"<p><p>The capacity to tolerate high G loads in the head-to-seat direction (+Gz tolerance) is critical for pilots flying high-performance aircraft. The adaptive effects of repeated +Gz loading on relaxed +Gz tolerance and G-protective sympathetic reflex pressor responses were investigated. Twelve men were exposed to increased +Gz loads in a relaxed state, during 15 × 40 min sessions across 5 wk. Before and after the training regimen, relaxed +Gz tolerance was investigated during rapid onset-rate (ROR) and gradual onset-rate (GOR) G exposures, and cardiovascular responses were investigated during exposures to 2.5 G in the belly-to-back direction (+Gx) as well as during orthostatic provocations and pressure manipulations of the carotid baroreceptors. The G training increased (<i>P</i> = 0.04) the ROR G tolerance by 17% but did not affect GOR G tolerance, orthostatic tolerance, or the sensitivity and operational pressure range of the carotid baroreflex pressor response. The training reduced (<i>P</i> < 0.001) the arterial pressure response to +Gx exposure. The results suggest that repeated high +Gz exposures do not improve the overall vascular sympathetic response to high +Gz nor the responsiveness of the vascular branch of the carotid baroreflex, but, judging by the arterial pressure responses to +Gx loads, reduces the responsiveness of the vestibulosympathetic reflex. That the G training improved the ROR +Gz tolerance is attributable to local vascular adaptation, in terms of increased stiffness in dependent precapillary vessels resulting from the iterative increments in local transmural pressures.<b>NEW & NOTEWORTHY</b> Five weeks of repeated exposures to head-to-seat directed G load in the relaxed state increased the capacity to tolerate rapid but not gradual G elevations, suggesting unaffected overall vascular sympathetic responses to high G. The G training did not affect the responsiveness of the vascular branch of the carotid baroreflex but reduced the vestibulosympathetic reflex response. The improved tolerance to rapid G elevations is attributable to increased stiffness in dependent precapillary vessels.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R86-R97"},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956273","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 effect of sex on the cardiopulmonary and neuromuscular response to high-intensity interval exercise.","authors":"Hannah K Wilson, Lina Bernert, Padraig Spillane, Emma Squires, Lorna Crawford, Jessica Piasecki, Ross Julian, Eurico N Wilhelm, Kirsty M Hicks, Paul Ansdell","doi":"10.1152/ajpregu.00306.2024","DOIUrl":"10.1152/ajpregu.00306.2024","url":null,"abstract":"<p><p>Sex differences exist in the integrative response to exercise; however, these are typically researched during incremental and constant-load exercise. Interval exercise involves high-intensity efforts interspersed with recovery periods to repeatedly stress physiological systems, and it is currently unknown whether the response to this form of exercise differs between sexes. Ten males and 10 females (age: 25 ± 3 yr) completed two experimental visits. First, an incremental treadmill exercise test was performed to obtain submaximal (lactate threshold) and maximal (V̇o_2peak) data. Thereafter, visit two involved 4 × 3-min running intervals at 90% of the final incremental test velocity (vV̇o_2peak), with 90-s rest between intervals. Before exercise and after each interval, maximal voluntary contraction (MVC), quadriceps potentiated twitch (<i>Q</i>_tw.pot), and voluntary activation (VA) were recorded. The rates of oxygen uptake (V̇o₂), carbon dioxide production (V̇co₂), and ventilation (V̇e) were continuously recorded throughout. There was no sex difference in relative V̇o_2peak (males: 47.2 ± 6.0 vs. females: 44.4 ± 5.8 mL·kg^-1·min^-1, <i>P</i> = 0.292). When expressed relative to peak values, there were no sex differences in the V̇o₂ or V̇co₂ response to the interval task (<i>P</i> ≥ 0.781). Females had greater V̇e/V̇o₂, and V̇e/V̇co₂ values during the first (<i>P</i> ≤ 0.034) and second (V̇e/V̇co₂, <i>P</i> = 0.006) intervals, with a sex × time interaction effect (<i>P</i> ≤ 0.046). There were no sex differences in the reductions in MVC, <i>Q</i>_tw.pot, and VA during the interval task (<i>P</i> ≥ 0.150); however, females had lesser reductions in <i>Q</i>_tw.pot values postexercise (-24 ± 9 vs. -15 ± 8%, <i>P</i> = 0.044). Sex differences exist in the physiological response to interval exercise. Compared with males, females experienced greater hyperpnea during the initial stages, and had lesser decreases in contractile function postexercise.<b>NEW & NOTEWORTHY</b> This study determined that males and females differ in the physiological response to high-intensity interval exercise. Specifically, females had poorer ventilatory efficiency during the first half of the task, but greater knee-extensor fatigue resistance following the task. These data build upon previous observations from constant-load exercise, demonstrating that physiological sex differences are observed during an ecologically valid exercise task commonly prescribed by practitioners in clinical and athletic populations.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R123-R133"},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101190","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 influence of aortic compliance on pulsatile cerebral blood flow in young healthy men: insight from endurance training intervention.","authors":"Tsubasa Tomoto, Hiroshi Kumagai, Takashi Tarumi, Jun Sugawara","doi":"10.1152/ajpregu.00038.2025","DOIUrl":"10.1152/ajpregu.00038.2025","url":null,"abstract":"<p><p>Aortic compliance reflects the ability to buffer arterial pulsations generated by the left ventricle (LV) and attenuate pulsatile cerebral blood flow (CBF). Endurance training is associated with increased stroke volume (SV) and enhanced LV systolic function, potentially increasing arterial pulsations to the brain. This study investigated the contribution of aortic compliance to the heart-brain hemodynamic interaction, providing insights from endurance training intervention and lower body negative pressure (LBNP) stimulus. Ten male collegiate tennis players underwent an 8-mo endurance training program to improve cardiac function. SV and LV systolic functions were measured using echocardiography and applanation tonometry. Pulsatile cerebral blood velocity in the middle cerebral artery was assessed by transcranial Doppler. Aortic compliance was calculated as the ratio between estimated SV via Modelflow and aortic pulse pressure via transfer function from radial arterial pressure. The release of -30 mmHg LBNP was used to initiate a rapid recovery of limited venous return and consequent increases in SV and CBF to assess dynamic recovery slopes. Endurance training increased SV, LV systolic function, and aortic compliance at rest, whereas pulsatile CBF was unchanged. The recovery slopes of SV and aortic compliance were steeper after endurance training, whereas the slopes of pulsatile CBF remained similar. The change in the slope of aortic compliance was negatively correlated with the change in the slope of pulsatile CBF (<i>r</i> = -0.758, <i>P</i> = 0.011). These results suggest that improved aortic compliance after endurance training may accommodate increased SV and LV systolic function and buffer potential increases in arterial pulsations to the brain.<b>NEW & NOTEWORTHY</b> Eight months of progressive moderate-to-vigorous endurance training increased stroke volume (SV), left ventricular (LV) systolic performance, and aortic compliance, whereas pulsatile cerebral blood flow (CBF) remained unchanged in young, healthy men. The increase in aortic compliance was associated with decreased pulsatile CBF. These findings suggest that the improved aortic compliance after endurance training may offset the expected increases in pulsatile CBF induced by the increased SV and enhanced LV systolic function.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R204-R215"},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257135","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":"Association between heart rate fragmentation and kidney function decline in MESA: evidence consistent with parasympathetic degradation.","authors":"Madalena D Costa, Susan Redline, Nisha Bansal, Susan R Heckbert, Ary L Goldberger","doi":"10.1152/ajpregu.00091.2025","DOIUrl":"10.1152/ajpregu.00091.2025","url":null,"abstract":"<p><p>The contribution of sympathetic overactivity to the pathogenesis of chronic kidney disease (CKD) is well established; in contrast, the role of the parasympathetic system in renal homeostasis remains less well understood. Studies in animal models suggest that parasympathetic activity may influence kidney function by buffering sympathetic tone, activating the cholinergic anti-inflammatory pathway, and modulating cardiovascular (CV) function. We investigated whether a novel noninvasive marker of parasympathetic function, heart rate fragmentation (HRF), was associated with <i>1</i>) the likelihood of prevalent CKD and <i>2</i>) longitudinal changes in estimated glomerular filtration rate (eGFR) over ∼5 yr. The analytical cohort included 1,388 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) (mean age: 66.8 ± 8.5 yr; 44.5% male) with polysomnographic ECG recordings. Higher HRF, indicative of reduced parasympathetic function, was associated with <i>1</i>) an increased likelihood of prevalent CKD (rate ratio: 1.15 [95% confidence interval (CI): 1.04; 1.27], per 1-SD increase in HRF) and <i>2</i>) a steeper decline in eGFR (-0.86 [95% CI: -1.43; -0.28] mL/min/1.73 m², per 1-SD increase in HRF), independent of major comorbidities, including age, hypertension, diabetes, and baseline CKD status. Stratified analyses in lower- and higher-risk subgroups yielded consistent results. These findings support a role for parasympathetic activity in renal homeostasis and suggest that HRF may serve as a noninvasive biomarker of risk for <i>1</i>) early renal function decline in lower-risk populations and <i>2</i>) accelerated decline in the general and higher-risk populations. HRF may also be useful for evaluating interventions targeting renal neuroautonomics, such as vagal stimulation or renal sympathetic denervation.<b>NEW & NOTEWORTHY</b> This study identifies reduced cardiac parasympathetic activity, measured by heart rate fragmentation (HRF), as a potential contributor to accelerated renal function decline in a community-based population. The findings suggest a mechanistic link between vagal dysfunction and kidney deterioration. From a translational perspective, the results support the utility of HRF-a noninvasive, repeatable measure-for renal disease risk stratification and monitoring of autonomic-targeted interventions.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R186-R194"},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12236214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186257","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}