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

{"title":"Exercise pressor reflex function is augmented in rats with chronic kidney disease.","authors":"Han-Kyul Kim, Juan A Estrada, Ayumi Fukazawa, Amane Hori, Gary A Iwamoto, Scott A Smith, Masaki Mizuno, Wanpen Vongpatanasin","doi":"10.1152/ajpregu.00234.2024","DOIUrl":"10.1152/ajpregu.00234.2024","url":null,"abstract":"<p><p>Cardiovascular responses to exercise are exaggerated in patients with chronic kidney disease (CKD). Enhanced sympathetic activation is thought to play a role with the exercise pressor reflex (EPR), a reflex originating in contracting muscle, modulating this response. Previous studies suggest an overactive EPR in patients with CKD as indicated by muscle sympathetic overactivation during static handgrip exercise. However, the role of the EPR could not be fully elucidated due to experimental constraints inherent to humans. The purpose of this study was to specifically test EPR function in a CKD animal model. Male Sprague-Dawley rats were assigned to a diet containing 0.25% adenine to induce CKD or a control diet. Mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) responses to activation of the EPR, including its functional components, the mechanoreflex and metaboreflex, were assessed in decerebrate, unanesthetized animals after feeding 10-14 wk. Plasma creatinine was significantly higher in CKD rats compared with controls (1.80 ± 0.78 vs. 0.34 ± 0.02 mg·dL^-1, <i>P</i> = 0.017). MAP and RSNA responses to muscle contraction (i.e., EPR activation) were potentiated in CKD rats compared with controls (Δ = 36 ± 19 vs. 17 ± 8 mmHg, <i>P</i> = 0.014 and Δ = 159 ± 62 vs. 64 ± 54%, <i>P</i> = 0.004, respectively). Similarly, the pressor and sympathetic responses to passive muscle stretch (i.e., mechanoreflex stimulation) were significantly higher in CKD than in control animals. Intra-arterial capsaicin administration (i.e., metaboreflex activation) induced an augmented pressor response in CKD rats, compared with controls. Our findings suggest that the EPR, stimulated by the mechanoreflex and metaboreflex, is exaggerated in CKD.<b>NEW & NOTEWORTHY</b> The current investigation identifies that activation of the exercise pressor reflex (EPR) by hindlimb muscle contraction generates exaggerated pressor responses in a chronic kidney disease (CKD) animal model. This hypertensive response is accompanied by sympathetic overactivation during EPR stimulation, with both the muscle mechanoreflex activated by passive muscle stretch and the muscle metaboreflex stimulated by intra-arterial capsaicin administration, contributing to the heightened pressor effect. These findings suggest augmented EPR, mechanoreflex, and metaboreflex function in CKD.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R460-R469"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490567","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":"Identification and analysis of amino acid metabolism-related subtypes in lung adenocarcinoma.","authors":"Yifan Zhou, Qiangchang Lu","doi":"10.1152/ajpregu.00217.2024","DOIUrl":"10.1152/ajpregu.00217.2024","url":null,"abstract":"<p><p>We aimed to explore the role of amino acid metabolism (AAM) and identify biomarkers for prognosis management and treatment of lung adenocarcinoma. Differentially expressed genes (DEGs) associated with AAM in lung adenocarcinoma were selected from public databases. Samples were clustered into varying subtypes using ConsensusClusterPlus based on gene levels. Survival analysis was conducted using a survival package, and immune analysis was performed using ssGSEA and ESTIMATE. Enrichment analysis was performed using gene set enrichment analysis, and a protein-protein interaction network of DEGs between subgroups was established through STRING. Hub genes were screened and verified using survival analysis, and drug sensitivity prediction was performed. One hundred sixty-three DEGs associated with AAM in lung adenocarcinoma were obtained, and two AAM-associated subtypes were identified. <i>Cluster 1</i> showed higher survival rates and immune levels compared with <i>cluster 2</i>. The two subtypes were mainly enriched in immune-related signaling pathways, such as B cell receptor, Jak-Stat, and natural killer cell-mediated cytotoxicity. In addition, the mutation landscape between the two groups was significantly different. F2, AHSG, and APOA1 were key hub genes that significantly affected the prognosis differences between the two subtypes. <i>Cluster 2</i> showed higher sensitivity to drugs, such as mithramycin, depsipeptide, and actinomycin than <i>cluster 1</i>. This study identified two AAM-associated gene subtypes and their biomarkers and predicted the immune status and drug treatment sensitivity of varying subtypes. The results are instructive in the clinical treatment of lung adenocarcinoma.<b>NEW & NOTEWORTHY</b> Two amino acid metabolism-related subtypes were identified based on differentially expressed genes associated with amino acid metabolism. <i>Cluster 1</i> showed higher survival rates and immune levels compared with <i>cluster 2</i>. <i>Cluster 2</i> showed higher sensitivity to drugs, such as mithramycin, depsipeptide, and actinomycin compared with <i>cluster 1</i>.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R470-R480"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913687","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":"Breaking the cycle: examining the role of endogenous and exogenous sex hormones on arterial stiffening in premenopausal women with PTSD.","authors":"Emily A Larson, Kerrie L Moreau","doi":"10.1152/ajpregu.00051.2025","DOIUrl":"10.1152/ajpregu.00051.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R506-R508"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new link between low testosterone and cardiovascular disease risk.","authors":"Grace S Maurer, Anna E Stanhewicz","doi":"10.1152/ajpregu.00043.2025","DOIUrl":"10.1152/ajpregu.00043.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R492-R493"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603535","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":"Heat-producing thermoeffector plasticity in response to prolonged iterative exposure to a high-heat loss environment: no indication of thermoregulatory fatigue.","authors":"Maaike I Moes, Antonis Elia, Ola Eiken, Michail E Keramidas","doi":"10.1152/ajpregu.00310.2024","DOIUrl":"10.1152/ajpregu.00310.2024","url":null,"abstract":"<p><p>Previous studies have suggested that, during prolonged cold exposure, shivering thermogenesis may gradually be attenuated, supposedly reflecting a state of central fatigue (aka 'thermoregulatory fatigue') provoked by extended shivering activity, that precipitates hypothermia. The purpose of this study was to revisit the validity of this notion. Twelve noncold-acclimatized men participated in three ∼10-h sessions, during which they performed repeatedly three 120-min cold-water immersions. To induce discrete amounts of heat-producing thermoeffector output, presumptively leading to distinct levels of fatigue during each session, subjects were submersed, within each session, in either severely (15°C), moderately (20°C), or slightly (28°C) cold water. The cold-induced elevation in thermogenic rate was similar across the three repeated immersions performed within the 15°C (∼130 W·m²) and 20°C (∼100 W·m²) sessions (<i>P</i> ≥ 0.43). In the 28°C-session, the metabolic heat production was augmented by ∼7% in the second and third immersions compared with the first immersion (<i>P</i> = 0.01). No intrasession differences were noted with regards to the body-core cooling rate, the cold-induced drop in skin temperature and forearm cutaneous vascular conductance, or the stress-hormone (salivary α-amylase and cortisol concentrations) and thermoperceptual responses (<i>P</i> > 0.05). The present findings, therefore, demonstrate that the ability to generate heat remains intact during prolonged iterative exposure to a high-heat loss environment in a single day, regardless of the severity of cold stressor. The intermittent application of slight cold stress (i.e., 28°C water) appears to mediate metabolic sensitization, reflecting either the circadian rhythmicity of heat-producing thermoeffector activity, or perhaps the rapid induction of metabolic adaptation.<b>NEW & NOTEWORTHY</b> The study evaluated whether centrally mediated thermoregulatory fatigue is provoked by prolonged exposure to uncompensable cold. Regardless of the severity of cold stressor, the ability to produce endogenous heat remains intact during prolonged iterative exposure to a high-heat loss environment.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R433-R446"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466665","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":"IL-6 induces mitochondrial ROS production and blunts NO bioavailability in human aortic endothelial cells.","authors":"Prema Velusamy, David J Buckley, Jody L Greaney, Adam J Case, Paul J Fadel, Daniel W Trott","doi":"10.1152/ajpregu.00289.2024","DOIUrl":"10.1152/ajpregu.00289.2024","url":null,"abstract":"<p><p>Chronic inflammation is a major contributor to the development of endothelial dysfunction. Circulating concentrations of the proinflammatory cytokine interleukin-6 (IL-6) have been shown to predict cardiovascular disease risk and are associated with the development of vascular dysfunction. However, the mechanisms that underlie inflammation-induced endothelial dysfunction are not fully understood. Vascular endothelial dysfunction is characterized by blunted nitric oxide (NO) bioavailability and increased reactive oxygen species (ROS), with mitochondrial ROS suggested to play a primary role. Therefore, we tested the hypothesis that IL-6 induces mitochondrial ROS production and blunts NO bioavailability in endothelial cells. To study the effect of IL-6, we treated the human aortic endothelial cells (HAECs) with IL-6, MitoTEMPOL (MT; a mitochondria-targeted antioxidant), and/or a nitric oxide synthase (NOS) inhibitor (l-NAME) with and without ACh stimulation. Results are expressed as means ± SD (<i>n</i> = 4 replicates), one-way ANOVA, and Bonferroni's post hoc tests were performed. IL-6 treatment resulted in greater mitochondrial ROS (IL-6: 2.94 ± 0.93 a.u.) when compared with the untreated cells (Control: 1 ± 0; <i>P</i> = 0.0021) and also blunted NO bioavailability at baseline (Control: 1 ± 0; IL-6: 0.57 ± 0.08 a.u. <i>P</i> = 0.0008) and with acetylcholine stimulation (Control Ach: 1.27 ± 0.09; IL-6 Ach: 0.60 ± 0.13 a.u. <i>P</i> < 0.0001). Scavenging mitochondrial ROS with MT restored NO bioavailability in the IL-6-treated cells (IL-6: 0.57 ± 0.08; IL-6 MT: 1.16 ± 0.20 a.u. <i>P</i> < 0.0001). These findings indicate that IL-6 has a direct effect on mitochondrial ROS in human aortic endothelial cells, which leads to reduced nitric oxide bioavailability.<b>NEW & NOTEWORTHY</b> In this study, we provide evidence that IL-6 induces mitochondrial ROS production, which impairs nitric oxide bioavailability in human aortic endothelial cells. This finding adds an important perspective to the existing literature on the mechanism by which IL-6 contributes to endothelial dysfunction.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R509-R514"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699400","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":"Possible Role of Muscle AMP Deamination: Focus on \"Skeletal Muscle Inosine Monophosphate Formation Preserves ∆GATP During Incremental Step Contractions in Vivo\".","authors":"Jerzy A Zoladz, Joanna Majerczak, Bernard Korzeniewski","doi":"10.1152/ajpregu.00030.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00030.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727474","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":"MLO-Y4 Fluid Flow Shear Stress Conditioned Media Enhances Cardiac Contractility and Intracellular Ca².","authors":"Anuhya Dayal, Mark Gray, Julian A Vallejo, Nuria Lara Castillo, Mark L Johnson, Michael J Wacker","doi":"10.1152/ajpregu.00287.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00287.2024","url":null,"abstract":"<p><p>The skeleton is in complex interplay with the other systems of the body and is highly responsive to input from the external environment. Bone mechanical loading results in interstitial fluid flow via the lacunar canalicular system, generating fluid flow sheer stress (FFSS). FFSS variably stresses osteocytes, subsequently causing the release of metabolites and protein factors which function locally to increase bone formation and may play a role in crosstalk between various organ systems, for instance between bone and skeletal muscle. Therefore, we hypothesized that this crosstalk includes altering cardiac function. To test this hypothesis, media conditioned by MLO-Y4 osteocyte-like cell culture line under FFSS was used to model the endocrine effects of bone during mechanical loading on contraction of ex vivo Langendorf-perfused isolated hearts. When hearts were externally paced at a fixed rate, FFSS osteocyte conditioned media (CM) induced significant premature contractions compared to vehicle (control). FFSS osteocyte CM administration to self-paced hearts increased total contraction force by 31%. To determine if the mechanism involved intracellular Ca²⁺, vehicle and FFSS bone CM were perfused over cultured H9C2 cardiomyocytes while undergoing Ca²⁺ imaging using Fluo-8. We observed an increase in intracellular Ca²⁺ with FFSS CM perfusion of cardiomyocytes compared to vehicle. These increases were only present with exogenous electrical pacing. Our findings demonstrate that FFSS bone CM enhances cardiac contractility by increasing intracellular cardiomyocyte Ca²⁺. The results obtained in this study suggest that the skeleton, responding to mechanical strain, has the potential to augment cardiac output and provide evidence for bone-heart crosstalk.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708226","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 anorexigenic peptide nesfatin-1 dampens the B cell response to receptor mediated stimulation through inhibition of NFĸB signaling.","authors":"Tara Steffen, Joshua D Stafford, Colleen R Bocke, Willis K Samson, Gina L C Yosten","doi":"10.1152/ajpregu.00233.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00233.2024","url":null,"abstract":"<p><p>Nesfatin-1, a post translational product of the protein encoded by the nucleobindin 2 gene (NUCB2), was functionally identified as an appetite regulatory molecule in rat hypothalamic nuclei. In the years following the discovery, those findings have been corroborated and expanded upon, and we now know that nesfatin-1 is expressed throughout peripheral tissues and exerts physiological effects beyond feeding control. Literature indicates that adipose tissue is one of the peripheral sources of NUCB2/nesfatin-1, and in this setting, it has anti-inflammatory effects that have recently been implicated in regulating chronic inflammation associated with diet induced obesity. Currently, there are gaps in our understanding of what cell types within the adipose tissue compartment respond to nesfatin-1, in addition to the cellular mechanism(s) of this peptide. In this study, we sought to determine a mechanism by which this peptide might directly interact with the immune system starting with a human B cell line, Raji. We show that nesfatin-1 inhibits lipopolysaccharide (LPS) and B cell receptor (BCR) dual stimulation-mediated B cell growth, stimulation induced cell death, and secretion of inflammatory mediators. Specifically, there was a reduced fold-change in B cell growth during stimulation which is paired with a reduction in the formation of apoptotic (annexin V⁺) cells. Additionally, nesfatin-1 significantly reduced IgM secretion and modestly reduced TNFα secretion by stimulated B cells. The anti-inflammatory effects of nesfatin- 1 overall are likely due to attenuation of NFĸB signaling, via inhibition of IĸB degradation, in stimulated B cells.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708230","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":"Serum cytokines and their soluble receptors are differently regulated between trained and untrained men after vigorous endurance exercise.","authors":"Jeremy B Ducharme, Jonathan W Specht, Alyssa R Bailly, Michael R Deyhle","doi":"10.1152/ajpregu.00010.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00010.2025","url":null,"abstract":"<p><p>Endurance training contributes to immune system changes that help manage exercise-induced stress and promote an anti-inflammatory effect. However, the specific mechanisms underlying these adaptations are still being explored. Cytokines play a key role in both acute and chronic exercise responses through interactions with their receptors, which are present in both membrane-bound and soluble forms. Yet, the impact of exercise on cytokines and soluble cytokine receptors in parallel remains understudied. Therefore, the purpose of this study was to assess how cytokines and their soluble receptors change in serum after vigorous exercise in endurance-trained and untrained men. Following 1-hour of cycling at their respiratory compensation point, untrained men (n=5) exhibited a significant increase in pro-inflammatory cytokines, including IL-6, TNF-α, IL-1β, CCL2, and VEGFA. In contrast, anti-inflammatory cytokines such as IL-10 and IL-1Ra were reduced. These effects were not observed in the trained group (n=7). Instead, pro-inflammatory cytokine levels remained close to baseline, while the anti-inflammatory cytokines IL-10 and IL-1Ra increased. In the trained group, these cytokine changes were accompanied by a marked increase in the expression of soluble cytokine receptors known to inhibit cytokine-mediated signaling, such as sIL-1RII, sGP130, sTNFRI, sTNFRII, sVEGFR1, and sVEGFR2, indicating reduced cytokine bioavailability. However, in the untrained group, the expression of these soluble cytokine receptors either remained unchanged or decreased, suggesting greater cytokine bioavailability. Together these findings highlight a novel potential anti-inflammatory adaptation such that trained men present a blunted inflammatory response by both reduced inflammatory cytokines and increased soluble cytokine receptors post45 exercise compared to untrained men.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699402","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}