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

{"title":"Endogenous muscarinic acetylcholine receptor signaling blunts α₁-adrenergic vasoconstriction during higher-intensity handgrip exercise in humans.","authors":"Janée D Terwoord, Frank A Dinenno, Jennifer C Richards, Christopher M Hearon","doi":"10.1152/ajpregu.00305.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00305.2024","url":null,"abstract":"<p><p>Muscarinic acetylcholine receptors (mAChRs) are expressed ubiquitously in the human skeletal muscle vasculature. Prior studies have been unable to identify a contribution of mAChR signaling to exercise-mediated vasodilation; however, no studies have determined whether endogenous mAChR signaling regulates the ability of contracting skeletal muscle to attenuate sympathetic vasoconstriction, a phenomenon called \"functional sympatholysis.\" We tested the hypothesis that endogenous mAChR signaling contributes to functional sympatholysis in humans. In healthy volunteers (8 F, 8 M; 26 ± 5 yr), changes in forearm vascular conductance (ΔFVC) were calculated in response to intra-arterial infusions of phenylephrine (PE; α₁-agonist) during <i>1</i>) infusion of a \"nonmetabolic\" vasodilator at rest (rest; adenosine or sodium nitroprusside), <i>2</i>) dynamic handgrip exercise at 15% maximal voluntary contraction (MVC), and <i>3</i>) higher-intensity exercise (25% MVC). Conditions were completed before and after intra-arterial infusion of atropine (mAChR antagonist). Under control conditions, vasoconstriction to PE was limited in parallel with exercise intensity (PE-induced %ΔFVC, rest: -40 ± 13%, 15% MVC: -20 ± 7%, 25% MVC: -12 ± 8%; <i>P</i> < 0.0001). There was no effect of atropine on PE vasoconstriction during rest (-38 ± 12%; <i>P</i> = 0.60 vs. control) or 15% MVC exercise (-23 ± 7%, <i>P</i> = 0.34 vs. control). However, PE-mediated vasoconstriction was approximately twofold greater during 25% MVC exercise after blockade of mAChRs (-22 ± 9%, <i>P</i> < 0.001 vs. control). These results provide evidence of a novel physiological role of endogenous mAChR signaling as a modulator of α₁-adrenergic vasoconstriction during higher-intensity handgrip exercise in humans.<b>NEW & NOTEWORTHY</b> The present study demonstrates that muscarinic acetylcholine receptor (mAChR) signaling attenuates postjunctional α₁-adrenergic signaling during higher-intensity exercise specifically within contracting skeletal muscle, thereby revealing endogenous mAChR signaling as a potential mechanism of functional sympatholysis. This is the first study to identify an endogenous signaling pathway that selectively modulates α₁-adrenergic vasoconstriction specifically in contracting muscle in humans. These findings establish a novel physiological role for endogenous mAChR signaling in the regulation of muscle blood flow during exercise.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":"328 6","pages":"R619-R627"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965954","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 exposure, heat strain, and off-work recovery of Guatemalan sugarcane workers.","authors":"Lyndsay Krisher, Karely Villarreal Hernandez, Yaqiang Li, Jaime Butler-Dawson, Diana Jaramillo, Hillary A Yoder, Kevin E Miller, Evan C Johnson, Katherine A James, Miranda Dally, Elizabeth J Carlton, Daniel Pilloni Alessio, Alex Cruz, Joshua Schaeffer, John L Adgate, Lee S Newman","doi":"10.1152/ajpregu.00004.2025","DOIUrl":"10.1152/ajpregu.00004.2025","url":null,"abstract":"<p><p>Agricultural workers are at high risk for heat-related illnesses when performing heavy labor in hot conditions. Occupational heat strain, the physiological response to heat stress, is hypothesized to be common in this worker population but has rarely been measured objectively through core body temperature (T_c). The objective of this study was twofold: <i>1</i>) evaluate workday heat strain and <i>2</i>) examine the trajectory of heat exposure and T_c from the workday through the off-work hours to advance understanding of the recovery process and conditions of heat-exposed agricultural workers. Among 55 male Guatemalan agricultural workers, individual heat exposure (using ambient temperature loggers) and T_c (via an ingestible pill) were measured across a 24-h period, including workday and off-work hours. Urine samples were collected to assess hydration status on and off-work. Workers reported off-work activities, hydration practices, sleep, and nutrition through a survey. Data were summarized using descriptive statistics and visualizations. Workers experienced excessive heat strain (44% with T_c > 38.0°C, 16% with T_c > 38.3°C, and 6% with T_c > 38.5°C) during the workday. Approximately 29% achieved a higher maximal T_c during off-work hours than during the workday. Nearly 15% of workers reported sleeping <7 h. There is a need to understand off-work conditions, practices, and resources available to workers to mitigate heat strain and related illnesses. Heat stress and T_c monitoring should extend to postwork shift for assessment of workers' physiological recovery and to inform more comprehensive interventions to protect worker health.<b>NEW & NOTEWORTHY</b> This study examined the trajectory of heat exposure and core body temperature (T_c) across the workday into off-work hours among agricultural workers at risk of heat-related illness. Workday heat strain was common, and a significant proportion of workers experienced higher off-work T_c compared with their workday T_c. Survey and environmental data collected from workers provide insights into the off-work practices and conditions of the home environment that could influence the recovery of workers.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R703-R717"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794348","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":"Inhibition of CYP450 pathways reduces functional sympatholysis in healthy young adults.","authors":"Alexander A Buelow, Jacob E Matney, Sarah M Skillett, John D Ashley, Jiwon Song, Chris Mixon, Amir Akbari Fakhrabadi, Matthew Stanford, Debra A Bemben, Daniel J Larson, J Mikhail Kellawan","doi":"10.1152/ajpregu.00173.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00173.2024","url":null,"abstract":"<p><p>Functional sympatholysis, the blunting of sympathetic vasoconstriction during exercise, is critical for regulating exercise hyperemia. The role of cytochrome P450-2C9 (CYP450) pathways in functional sympatholysis remains unclear. A total of 21 participants (11 females) completed three study visits (2 experimental). Participants ingested a placebo (PLA) or CYP450 inhibitor fluconazole (FLZ) 120 min before testing in a double-blind, randomized, crossover design. Forearm blood flow (FBF) and mean arterial pressure (MAP) were continuously measured to calculate forearm vascular conductance (FVC) during baseline, -20 mmHg lower body negative pressure (LBNPrest), rhythmic handgrip exercise (Ex) at 20% maximum voluntary contraction, and exercise with LBNP (LBNPex). FLZ did not change FVC at baseline or during Ex (<i>P</i> > 0.05). However, adding LBNPex to Ex reduced FVC in the FLZ condition compared with PLA (PLA: 2 ± 12 Δ% vs. FLZ: -12 ± 13 Δ%, <i>P</i> < 0.001, <i>d</i>: 0.9). A significant change in FVC across time (baseline + LBNPrest vs. Ex + LBNPex) was observed (<i>P</i> < 0.001, [Formula: see text]: 0.8), along with significant effects of condition (PLA vs. FLZ) (<i>P</i>: 0.003, [Formula: see text]: 0.4) and their interaction (<i>P</i>: 0.05, [Formula: see text]: 0.2). Functional sympatholysis magnitude differed between conditions (PLA: 107 ± 41% vs. FLZ: 67 ± 50%, <i>P</i>: 0.001, <i>r</i>: 0.7). Therefore, CYP450 pathways are mechanistically involved in functional sympatholysis. However, CYP450 inhibition does not augment resting or exercising vascular responses without constrictor stimuli.<b>NEW & NOTEWORTHY</b> Evidence suggests that functional sympatholysis is an endothelial-dependent, nitric oxide and prostaglandin-independent process. We found that cytochrome P450-2C9 (CYP450-2C9) inhibition attenuated sympatholytic responses during dynamic handgrip exercise with superimposed lower body negative pressure. These data indicate that CYP450 pathways contribute to functional sympatholysis in young healthy humans.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":"328 6","pages":"R642-R650"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955886","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":"Evidence for HCO₃^- and NH₃/NH₄⁺-dependent pH regulatory mechanisms in the alkaline midgut of the sea urchin larva.","authors":"Inga Petersen, Sima Jonusaite, Femke Thoben, Marian Y Hu","doi":"10.1152/ajpregu.00222.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00222.2024","url":null,"abstract":"<p><p>Alkaline digestive systems are well described for some insect species and their larval stages. More recently, larvae of the members of ambulacraria superphylum consisting of echinoderms and hemichordates were also discovered to have highly alkaline midguts (pH 9.5-10.5) with the underlying acid-base regulatory mechanisms largely unknown. Using pharmacological inhibition of acid-base transporters in conjunction with ion-selective microelectrode measurements and pH-sensitive dyes, we investigated intracellular and extracellular pH regulatory mechanisms of midgut epithelial cells of a sea urchin (<i>Strongylocentrotus purpuratus</i>) larva. Our findings suggest that vacuolar-type H⁺-ATPase (inhibited by bafilomycin a1), carbonic anhydrase (inhibited by acetazolamide), anion-exchangers (inhibited by 4,4'-diisothiocyano-2,2'-disulfonic acid or DIDS), and soluble adenylyl cyclase (inhibited by KH7) play crucial roles in cellular acid-base regulation as well as midgut alkalization. Ammonia excretion rates were decreased in the presence of bafilomycin and colchicine, pointing toward vesicular [Formula: see text] trapping and exocytosis mechanism in eliminating nitrogenous proton equivalents from midgut cells. Finally, midgut perfusion studies revealed ouabain-sensitive luminal [Formula: see text] uptake, suggesting a role for Na⁺/K⁺-ATPase-mediated ammonia transport in midgut alkalization. This comprehensive pharmacological analysis provides a new working model relying on the CO₂/[Formula: see text] and NH₃/[Formula: see text] buffer systems for midgut alkalization in the sea urchin larva. These findings are discussed in the context of other alkalizing systems with strong implications for the conserved role of [Formula: see text] and NH₃-driven mechanism of midgut alkalization across the animal kingdom.<b>NEW & NOTEWORTHY</b> Sea urchin larvae evolved highly alkaline conditions in their digestive tracts, and the underlying acid-base regulatory mechanisms are little understood. Here we present evidence that the process of luminal alkalization is cAMP-dependent. Furthermore, our data point toward the involvement of bicarbonate and ammonia in regulating midgut fluid pH. These results identified a novel mechanism for luminal alkalization in the digestive tract of a marine animal with strong implications for other alkalizing systems in animals.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":"328 6","pages":"R685-R699"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963527","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 cardiac baroreflex function associated with cardiovascular disease?","authors":"Ryota Asahara, Shigehiko Ogoh","doi":"10.1152/ajpregu.00083.2025","DOIUrl":"10.1152/ajpregu.00083.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R727-R729"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952641","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":"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":"https://doi.org/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":"","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":"","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":"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":"","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":"","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":"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}