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

{"title":"Augmented analgesic effect of tyramine or octopamine in combination with lidocaine is mediated with α-adrenergic receptors.","authors":"An-Kuo Chou, Chong-Chi Chiu, Yu-Wen Chen, Ching-Hsia Hung, Jhi-Joung Wang","doi":"10.1152/ajpregu.00225.2024","DOIUrl":"10.1152/ajpregu.00225.2024","url":null,"abstract":"<p><p>Although norepinephrine is known to enhance the antinociceptive effect of the local anesthetic lidocaine, the effects of two precursors of norepinephrine, tyramine and octopamine, on the antinociceptive potency of lidocaine are not known. We aimed to investigate cutaneous antinociceptive interactions and mechanism of action of tyramine and octopamine, and their respective coinjections with lidocaine, in comparison with norepinephrine. Cutaneous nociceptive blockade in rats was quantified by the blockage of cutaneous trunci muscle reflexes induced by needle pinpricks. Isobolographic analysis was used to estimate the interactions between lidocaine and drugs (tyramine, octopamine, or norepinephrine). Phentolamine was added to a two-drug combination. At ED₇₅ (75% effective dose), subcutaneous injection of tyramine and lidocaine provoked 73% and 77% nociceptive blockade. After isobolographic analysis, the theoretical 50% effective dose (ED₅₀) was significantly greater than the experimental ED₅₀ in both octopamine-lidocaine combination and norepinephrine-lidocaine combination (<i>P</i> < 0.01), but not in tyramine-lidocaine combination. Lidocaine (ED₉₅) in combination with tyramine (30 µmole), octopamine (12 µmole), or norepinephrine (0.007 µmole) prolonged the duration of nociceptive blockade (<i>P</i> < 0.05). The addition of phentolamine (0.06 µmole) to a combination of tyramine (30 µmole) and lidocaine (ED₉₅), a combination of octopamine (12 µmole) and lidocaine (ED₉₅), or a combination of norepinephrine (0.007 µmole) and lidocaine (ED₉₅) showed a nociceptive blocking effect similar to that of lidocaine (ED₉₅) alone. Tyramine and octopamine presented dose-dependent cutaneous nociceptive blockades. Tyramine-lidocaine combination produced an additive effect. The combination of octopamine-lidocaine and norepinephrine-lidocaine showed synergistic effects that were inhibited by phentolamine, suggesting that this synergistic effect is mediated with α-adrenergic receptors.<b>NEW & NOTEWORTHY</b> Tyramine and octopamine prolonged the duration of cutaneous nociceptive blockades by lidocaine. We have identified a new mechanism that augmented analgesic effect of tyramine or octopamine in combination with lidocaine is mediated with α-adrenergic receptors.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R783-R790"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555506","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 role of nutritional factors in exercise-induced bronchoconstriction: a narrative review.","authors":"Abigail S Sogard, Travis S Emerson, Christopher A Chandler, Emily A Cobb, Ren-Jay Shei, Hunter L Paris, Martin R Lindley, Timothy D Mickleborough","doi":"10.1152/ajpregu.00249.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00249.2024","url":null,"abstract":"<p><p>Exercise-induced bronchoconstriction (EIB) describes an acute narrowing of the airways that develops following vigorous physical activity. Clinical responses to current asthma therapy, such as leukotriene antagonists and corticosteroids, are heterogeneous, even with optimal treatment. Epidemiological studies indicate an increasing use of complementary and alternative medicine therapy in asthma patients due to the lack of efficacy of conventional treatment, concerns about potentially harmful side effects of pharmacological treatment, cost barriers to asthma care, and the accessibility of complementary and alternative medicine therapy. Plausible physiological mechanisms now exist for many nutrients as potential modifiers of EIB severity, primarily because of their role in inflammatory processes, airway smooth muscle function, and modulation of lung microvascular volume and pressure. Dietary supplementation as a treatment for EIB has generally shown evidence of significant yet incomplete inhibition of EIB with low-salt diets, omega-3 fatty acids, and vitamin C when supplemented for up to 3 weeks. However, larger, randomized, placebo-controlled, double-blinded trials are needed to clarify the effectiveness of nutritional intervention in individuals with EIB. Additionally, many studies have focused on nonathletes with EIB, and therefore, more studies are required to evaluate the efficacy of nutritional intervention on EIB in elite athletes. In conclusion, if dietary supplementation or restriction is prescribed, it should be seen as an option to lessen the reliance on pharmaceutical interventions and not as an alternative to established pharmacotherapies.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":"328 6","pages":"R651-R684"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956006","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":"Reutericyclin mitigates risperidone-induced suppression of anaerobic energy expenditure.","authors":"Matthew A Hadiono, Alexis B Kazen, Fatima A Aboulalazm, Colin M L Burnett, John J Reho, Tammy L Kindel, Justin L Grobe, John R Kirby","doi":"10.1152/ajpregu.00190.2024","DOIUrl":"10.1152/ajpregu.00190.2024","url":null,"abstract":"<p><p>Recent studies from our laboratory demonstrated that the gut microbial community represents a thermogenic biomass, as cecectomy causes an ∼8% decrease in total energy expenditure (EE) via suppression of anaerobic EE. The composition of the microbial community also dictates the EE of the microbial biomass as treatment with the antipsychotic, risperidone, suppresses anaerobic EE in a microbiome-dependent manner. Finally, we have determined that a specialized metabolite produced by <i>Limosilactobacillus reuteri</i>, reutericyclin (RTC), opposes the weight-gain effects of risperidone. In the present study, we performed comprehensive evaluations of energy balance in female C57BL/6J mice treated with risperidone, RTC, or both, to identify mechanisms by which RTC affects energy balance to mitigate risperidone-induced weight gain. We observed that risperidone suppressed anaerobic EE, and that RTC coadministration ameliorated the anaerobic EE suppression and weight gain induced by risperidone. Because anaerobic EE is dependent on the gut microbiota, we performed 16S and whole genome shotgun sequencing on stool and cecal samples following whole animal calorimetry. Risperidone and RTC treatments reciprocally modified the relative abundance of taxa known to participate in fermentation, especially for the production of short-chain fatty acids, which have been correlated with health and leanness in both humans and mice. Together, our data demonstrate that treatment with RTC positively modulates anaerobic EE, possibly by enhancing fermentation of the gut microbial community, and may represent a novel therapeutic in the treatment of obesity.<b>NEW & NOTEWORTHY</b> The gut microbial community represents a thermogenic biomass. The composition of the microbial community dictates energy expenditure of the microbial biomass and is altered by xenobiotics and bacterial metabolites. This study demonstrates that treatment with reutericyclin positively modulates anaerobic energy expenditure and may represent a novel therapeutic in the treatment of obesity.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R741-R757"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965362","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":"GL261 glioblastoma induces delayed body weight gain and stunted skeletal muscle growth in young mice.","authors":"Joshua R Huot, Nicholas A Jamnick, Fabrizio Pin, Patrick D Livingston, Chandler S Callaway, Andrea Bonetto","doi":"10.1152/ajpregu.00035.2025","DOIUrl":"10.1152/ajpregu.00035.2025","url":null,"abstract":"<p><p>The survival rate for children and adolescents has increased to over 85%. However, there is limited understanding of the impact of pediatric cancers on muscle development and physiology. Given that brain tumors alone account for 26% of all pediatric cancers, this study aimed to investigate the skeletal muscle consequences of tumor growth in young mice. C2C12 myotubes were cocultured with GL261 murine glioblastoma cells to assess myotube size. GL261 cells were then injected subcutaneously into 4-wk-old male C57BL/6J mice. Animals were euthanized 28 days post-GL261 implantation. Muscle function was tested in vivo and ex vivo. Muscle protein synthesis was estimated via the SUnSET method, and gene/protein expression levels were assessed via Western blotting and qPCR. In vitro, the C2C12 cultures exposed to GL261 exhibited myotube atrophy, consistent with a disrupted anabolic/catabolic balance. In vivo, carcass, heart, and fat mass were significantly reduced in the tumor-bearing mice. Skeletal muscle growth was impeded in the GL261 hosts, along with a smaller muscle cross-sectional area (CSA). Both in vivo muscle torque and the ex vivo Extensor Digitorum Longus (EDL) muscle force were unchanged. At molecular level, the tumor hosts displayed reduced estimations of muscle protein synthesis and increased muscle protein ubiquitination, in disagreement with decreased muscle ubiquitin ligase mRNA expression. Overall, we showed that GL261 tumors impact the growth of pediatric mice by stunting skeletal muscle development, decreasing muscle mass, reducing muscle fiber size, diminishing muscle protein synthesis, and altering protein catabolism signaling.<b>NEW & NOTEWORTHY</b> This study shows that pediatric brain tumors stunt muscle development in young mice. GL261 glioblastoma cells caused myotube atrophy, reduced carcass, heart, and fat mass, and impeded skeletal muscle growth. Tumor-bearing mice had decreased muscle protein synthesis and increased protein ubiquitination. This is the first demonstration that GL261 tumors reduce muscle mass and fiber size, impair muscle function and innervation, and alter muscle protein turnover.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":"328 6","pages":"R628-R641"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955882","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":"Impact of surgical bladder catheter implantation on voiding function in mice.","authors":"Benjamin E Rubin, Margaret A Vizzard, Gerald M Herrera","doi":"10.1152/ajpregu.00300.2024","DOIUrl":"10.1152/ajpregu.00300.2024","url":null,"abstract":"<p><p>Lower urinary tract (LUT) disorders significantly impact quality of life, yet treatment advancements remain limited. Animal models, such as those using invasive urodynamics with surgically implanted suprapubic bladder catheters, are vital for preclinical research. However, the effects of catheter implantation on bladder function have not been well characterized. The primary objective of this study was to evaluate the impact of surgical bladder catheter implantation on voiding function in male and female mice by comparing noninvasive voiding behavior before and after bladder catheter implantation in the same animals. We assessed voiding parameters in 16 mice (<i>n</i> = 7 male and <i>n</i> = 9 female) before and after catheter implantation using noninvasive voiding assays conducted in a home-cage environment. These assessments revealed significant changes in postimplantation voiding behavior, characterized by increased void frequency (<i>P</i> = 0.0004) and decreases in both void volumes (<i>P</i> < 0.0001) and intermicturition intervals (<i>P</i> = 0.0006). Urodynamic studies further demonstrated that bladder capacities were reduced 10%-30% compared with preimplantation estimates, reflecting physical reductions in bladder volume caused by the catheterization procedure. Similar results in the voiding function were seen in both male and female mice. These findings demonstrate that surgical catheter implantation alters voiding function, with overall consistent effects observed across sexes. The observed changes likely result from physical bladder size reduction due to catheter placement and the use of a purse-string suture to secure the catheter. This study underscores the importance of accounting for procedural artifacts in preclinical LUT research to ensure translational relevance.<b>NEW & NOTEWORTHY</b> This study provides the first characterization of voiding behavior and bladder function changes following surgical bladder catheter implantation in mice, as measured using noninvasive assays. We show that surgical catheter implantation reduces bladder capacity and significantly alters voiding parameters, including frequency, volume, and intermicturition intervals, with overall consistent effects across sexes. These findings highlight the importance of accounting for procedural artifacts when interpreting LUT function in preclinical models, ensuring translational relevance for future studies.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R718-R726"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965359","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":"Swimming-induced cardioprotection and cardiac remodeling are a multi-organ affair.","authors":"Joseph Mannozzi","doi":"10.1152/ajpregu.00086.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00086.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":"328 6","pages":"R700-R702"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955620","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 Heckbert, Ary L Goldberger","doi":"10.1152/ajpregu.00091.2025","DOIUrl":"https://doi.org/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) the likelihood of prevalent CKD and (ii) longitudinal changes in estimated glomerular filtration rate (eGFR) over approximately five years. The analytical cohort included 1,388 MESA participants (mean age: 66.8 ± 8.5 yrs; 44.5% male) with polysomnographic ECG recordings. Higher HRF, indicative of reduced parasympathetic function, was associated with (i) an increased likelihood of prevalent CKD (rate ratio: 1.15 [95% CI: 1.04; 1.27], per one-SD increase in HRF) and (ii) a steeper decline in eGFR (-0.86 [95%CI: -1.43; -0.28] mL/min/1.73 m2, per one-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 (1) early renal function decline in lower-risk populations and (2) 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.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The molecular origin of body temperature in homeothermic species.","authors":"Gerhard M Artmann, Oliver H Weiergräber, Samar Damiati, Ipek Seda Firat, Aysegül Temiz Artmann","doi":"10.1152/ajpregu.00236.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00236.2024","url":null,"abstract":"<p><p>We propose the Interfacial Water Quantum-transition model (IWQ model) as a novel paradigm explaining temperature-dependent structural and functional transitions (discontinuities) observed in proteins. The central postulate states that experimentally measured critical temperatures, T_C, are related to physical reference temperatures, T_W, defined by rotational quantum transitions of temporarily free water molecules in the protein-water interface. Applicability of this concept is demonstrated using transitions observed in two disparate model systems, viz., hemoglobin and thermosensitive TRP channels. We propose that the same mechanism underlies the definition of basal body temperatures in homeotherms, the reference temperature for humans being T_W=36.32°C. Specifically, we demonstrate that the body temperatures of both human and chicken (representing the two classes of homeothermic vertebrates) not only coincide with quantum-transition reference temperatures but are also related to pronounced transitions in hemoglobin oxygen saturation. This suggests that the evolution of body temperatures in different homeothermic species might involve an interplay between critical parameters of oxygen supply on the one hand and quantum-physical rotational transition temperatures of water on the other. Casting the IWQ-model concept into a concise formula: Proteins sense and water sets critical physiological temperatures.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092497","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":"Is there a golden hour for exercise in ageing females? A perspective on the female-specific effects of oestradiol in regulating vascular endothelial function.","authors":"Hollie Speer, Joseph M Northey","doi":"10.1152/ajpregu.00163.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00163.2024","url":null,"abstract":"<p><p>Sex hormones are known for their roles in reproductive health; however, they pose auxiliary actions on non-reproductive tissues such as the vasculature, notably involving the mediation of endothelial vasodilation and vasoconstriction. Abrupt declines in oestrogen during the menopausal transition have been associated with endothelial dysfunction and a subsequent increase in cardiovascular events. It should come as no surprise that participation in physical activity and exercise are recommended as common strategies to enhance endothelial function, and the effectiveness of different exercise modalities on vascular health outcomes and risk modulation has been investigated extensively. However, despite the awareness of increased cardiovascular disease (CVD) risk during and after menopause, there is conflicting evidence surrounding the efficacy of exercise as a means to enhance endothelial function in females during this critical period. This perspective article intends to discuss the current evidence relating to the female-specific influence of oestradiol on endothelial function, and if there is potential to elicit greater vascular benefits of exercise in late reproductive age by intervening during perimenopause.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sympathetic Neural Overdrive, Vascular Dysfunction and Diminished Exercise Capacity in Long COVID-19 Patients: A Long-Term Study of Cardiovascular Sequelae.","authors":"Bruna E Ono, João E Izaias, Artur O Sales, Thais S Rodrigues, Camila S Nunes, Jessica F Niec, Natalia G Rocha, Helena N M Rocha, Gabriel F Teixeira, Amanda G Rodrigues, Carlos E Negrão, Maria C C Irigoyen, Fernanda M C Colombo, Antonio Viana Nascimento-Filho, Katia De Angelis, Robson A S Santos, Andreia M Porcari, Katelyn R Ludwig, Daniel H Craighead, Matthew J Rossman, Renata Moll-Bernardes, Douglas R Seals, Allan R K Sales","doi":"10.1152/ajpregu.00055.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00055.2025","url":null,"abstract":"<p><p><b>Background:</b> We have recently showed that severe COVID patients have neurovascular dysfunction, cardiac morpho-functional alterations, and attenuated exercise capacity. However, whether these alterations persist over time is unknown. Here, we tested the hypothesis that Long COVID patients, even 2 years after SARS-COV-2 infection, exhibit sympathetic overdrive, aortic stiffening, endothelium-dependent dysfunction, cardiac morpho-functional changes, and diminished exercise capacity. <b>Methods:</b> Eighteen Long COVID patients and 19 well-matched controls were studied. Muscle sympathetic nerve activity (MSNA; microneurography), brachial artery flow-mediated dilation (BAFMD; ultrasound-Doppler), carotid-femoral pulse wave velocity (CFPWV; tonometry), heart rate (HR; EKG), E/A ratio, left ventricular ejection fraction and global longitudinal strain (LVEF, LVGLS; echocardiography), and peak oxygen uptake (Peak V̇O₂, cardiopulmonary exercise testing) were assessed ⁓2 years after hospital discharge. Circulating angiotensin II (Ang II, mass spectrometry), endothelial cell-derived extracellular vesicles (endothelial cell-derived EVs, flow cytometry), and oxidative stress were also evaluated. <b>Results:</b> Long COVID patients had higher MSNA, CFPWV, HR and lower E/A ratio, LVEF, LVGLS and Peak V̇O₂ than controls. Endothelial cell-derived EVs and carbonyls were higher in Long COVID patients than controls, whereas superoxide dismutase (SOD) was lower. No difference was observed in Ang II. Peak V̇O₂ was inversely associated with MSNA, LVGLS and carbonyls, and directly associated with BAFMD and SOD. <b>Conclusions:</b> Our findings reveal that Long COVID patients, 2 years after acute illness, exhibit persistent sympathetic overactivation, vascular and cardiac impairments, reduced exercise capacity, and increased endothelial cell-derived EVs and oxidative stress. As such, strategies that can resolve these persistent cardiovascular sequelae are urgently needed.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970517","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}