Hypertension最新文献

{"title":"In Memoriam: Allyn L. Mark.","authors":"Gerald F DiBona, Donald D Heistad","doi":"10.1161/HYPERTENSIONAHA.125.25103","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.125.25103","url":null,"abstract":"","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"82 7","pages":"e108-e109"},"PeriodicalIF":6.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ca-circSCN8A Promotes HPASMCs Ferroptosis via LLPS Initiated R-Loop.","authors":"Mengnan Li, Yingying Hao, Xinyue Song, Huiyu Liu, Chi Zhang, Jiaqi Zhang, Hanliang Sun, Xiaodong Zheng, Lixin Zhang, Hang Yu, Cui Ma, Xijuan Zhao, Daling Zhu","doi":"10.1161/HYPERTENSIONAHA.125.25036","DOIUrl":"10.1161/HYPERTENSIONAHA.125.25036","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis has been implicated in pulmonary hypertension (PH), and chromatin-associated RNAs are increasingly recognized as key regulators of this process. However, the detailed mechanism remains unexplored.</p><p><strong>Methods: </strong>Bioinformatics, Sanger sequencing, and RNase R digestion were used to identify the upregulation of ca-circSCN8A. Functional gain and loss assays were used to unveil the role of ca-circSCN8A in hypoxic redox-dependent ferroptosis in human pulmonary arterial smooth muscle cells and a PH mice model. Interaction between ca-circSCN8A and FUS was detected via RNA immunoprecipitation and pull-down assays. Fluorescence recovery after photobleaching, ChIRP-qPCR (Chromatin Isolation by RNA Purification followed by Quatitative PCR), malondialdehyde, reduced glutathione, and glutathione were conducted to explore the potential molecular mechanism.</p><p><strong>Results: </strong>ca-circSCN8A was identified and confirmed to be upregulated in PH. Its overexpression promoted hypoxia-induced ferroptosis in human pulmonary arterial smooth muscle cells. Under hypoxic conditions, ca-circSCN8A recruited EP300 to facilitate the lactylation of FUS (Fused in Sarcoma), triggering the formation of a ca-circSCN8A/FUS/EP300 complex via liquid-liquid phase separation. Liquid-liquid phase separation maintained the stability of the R-loop formed by ca-circSCN8A and ferroptosis-related gene SLC7A11 (solute carrier family 7 member 11) promoter that inhibits its transcription, further result in the disruption of the redox homeostasis and causing ferroptosis in human pulmonary arterial smooth muscle cells.</p><p><strong>Conclusions: </strong>ca-circSCN8A recruits EP300 to promote the lactylation of FUS, thereby driving liquid-liquid phase separation-mediated complex formation with FUS and EP300. This process enables ca-circSCN8A to form an R-loop with the nonhost SLC7A11 promoter, contributing to the regulation of hypoxia-induced ferroptosis in human pulmonary arterial smooth muscle cells. This study provides the first evidence that circRNAs can form R-loops with nonhost genes in a liquid-liquid phase separation-dependent manner. Our findings highlight ca-circSCN8A as a crucial regulator of ferroptosis in hypoxic PH and a potential therapeutic target for PH.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"e114-e128"},"PeriodicalIF":6.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory Roles of Long Noncoding RNAs in Arterial Stiffness and Hypertension.","authors":"Jose D Vargas, Malak Abbas, Gabriel Goodney, Han Le, Antentor O Hinton, Amadou Gaye","doi":"10.1161/HYPERTENSIONAHA.124.23580","DOIUrl":"10.1161/HYPERTENSIONAHA.124.23580","url":null,"abstract":"<p><strong>Background: </strong>Arterial stiffness, commonly assessed via pulse wave velocity (PWV), is marked by reduced arterial elasticity and serves as a significant risk factor for cardiovascular disease and an early indicator of hypertension. This study investigated the regulatory roles of long noncoding RNAs (lncRNAs) in modulating mRNAs associated with arterial stiffness and hypertension, with a particular focus on African American individuals, a population disproportionately impacted by hypertension.</p><p><strong>Methods: </strong>We utilized whole-blood transcriptome sequencing data from 2 African American cohorts with high hypertension prevalence: the GENE-FORECAST (the Genomics, Environmental Factors, and Social Determinants of Cardiovascular Disease in African Americans Study; 436 subjects) and the MH-GRID study (Minority Health Genomics and Translational Research Bio-Repository Database; 179 subjects). Our objectives were to: (1) identify lncRNAs and mRNAs differentially expressed between the upper and lower tertiles of PWV; (2) determine differentially expressed lncRNAs associated with the expression levels of each differentially expressed mRNA; and (3) link the lncRNA-modulated mRNAs to hypertension across both data sets. For each of the 3 analyses, results were considered significant if the false discovery rate-adjusted <i>P</i> value was ≤0.05 in the discovery data set, the <i>P</i> value was ≤0.05 in the validation data set, and the effect size was consistent in direction across the 2 data sets.</p><p><strong>Results: </strong>Differential expression analysis revealed, respectively 1035 mRNAs and 31 lncRNAs differentially expressed between upper and lower PWV groups. Then, lncRNA-mRNA pairs significantly associated were identified, involving 31 unique lncRNAs and 1034 unique mRNAs. Finally, 22 of the lncRNA-modulated mRNAs initially linked to PWV were found to be associated with hypertension and replicated. Interestingly, 30 lncRNAs were linked to the expression of <i>UCP2</i> (Uncoupling Protein 2), a gene implicated in oxidative stress and endothelial function.</p><p><strong>Conclusions: </strong>Our findings underscore the significant roles of lncRNAs in regulating gene expression associated with arterial stiffness and hypertension. The differential expression of <i>UCP2</i> in relation to PWV and hypertension, along with its potential regulation by lncRNAs, offers valuable insights into the molecular mechanisms underlying arterial stiffness and its connection with hypertension.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"1195-1207"},"PeriodicalIF":6.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sympathetic Vasomotion Reflects Catheter-Based Radiofrequency Renal Denervation.","authors":"Peter Ricci Pellegrino, Irving H Zucker, Yiannis S Chatzizisis, Han-Jun Wang, Alicia M Schiller","doi":"10.1161/HYPERTENSIONAHA.125.24980","DOIUrl":"10.1161/HYPERTENSIONAHA.125.24980","url":null,"abstract":"<p><strong>Background: </strong>The field of renal denervation remains challenged by the inability to confirm successful ablation of the targeted renal sympathetic nerves. The availability of technology to measure regional blood flow in real-time makes sympathetic control of the renal vasculature a logical end point to assess effective renal denervation, but autoregulatory mechanisms mask effects on mean renal blood flow. We hypothesized that renal sympathetic vasomotion, a novel marker of rhythmic sympathetic control, reflects successive rounds of catheter-based radiofrequency renal denervation.</p><p><strong>Methods: </strong>To test this, 10 pigs underwent unilateral surgical renal denervation, recovered for at least 7 days, and then underwent 4 successive rounds of catheter-based radiofrequency denervation of the contralateral kidney. Bilateral renal blood flow velocity and abdominal aortic pressure were measured before and after ablations to calculate renal vasomotion.</p><p><strong>Results: </strong>Before catheter-based denervation, the renal vasomotion profiles of the innervated and surgically denervated kidneys differed significantly (<i>P</i><0.005). Ablation of the largest renal branch artery reduced renal sympathetic vasomotion by 52%. Ablation of the remaining renal branch arteries reduced sympathetic vasomotion by 95% from baseline and eliminated the statistical differences between surgically and catheter-denervated kidneys. Two additional rounds of catheter denervation of the main renal artery did not consistently decrease the renal sympathetic vasomotion magnitude any further.</p><p><strong>Conclusions: </strong>These results indicate that renal sympathetic vasomotion could provide intraprocedural feedback for interventionalists performing catheter-based renal denervation and thereby improve the efficacy, safety, and consistency of this antihypertensive intervention.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"1261-1270"},"PeriodicalIF":6.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of the Renin-Angiotensin System in Blood Pressure Regulation in Smooth Muscle-Specific Cullin-3 Deficient Mice.","authors":"Daria Golosova, Gaurav Kumar, Nisita Chaihongsa, John J Reho, Ko-Ting Lu, Daniel T Brozoski, Kelsey K Wackman, Samuel B R Lawton, Patricia C Muskus, Brian L Lin, Justin L Grobe, Pablo Nakagawa, Curt D Sigmund","doi":"10.1161/HYPERTENSIONAHA.125.25045","DOIUrl":"10.1161/HYPERTENSIONAHA.125.25045","url":null,"abstract":"<p><strong>Background: </strong>Selective ablation of CUL3 (Cullin-3) in vascular smooth muscle cell-selective CUL3 knockout (S-CUL3KO) results in severe hypertension with paradoxically unaltered ANG II (angiotensin II) levels, suggesting an increase in ANG II sensitivity. We hypothesized that the hypertension and vascular dysfunction in S-CUL3KO mice are mediated by an exaggerated calcium response to ANG II in vascular smooth muscle cells.</p><p><strong>Methods: </strong>Blood pressure was measured by radiotelemetry in S-CUL3KO mice subjected to pharmacological inhibition of the renin-angiotensin system. Vascular function was evaluated in several arterial beds, and freshly isolated smooth muscle cells were used to elucidate the contribution of CUL3 to ANG II-induced cytosolic calcium concentration flux. The involvement of potential calcium channels was evaluated based on gene expression in carotid arteries and pharmacological studies.</p><p><strong>Results: </strong>S-CUL3KO mice exhibited severe hypertension with an enhanced depressor response following the administration of renin-angiotensin system inhibitors. Candesartan administration before induction of the CUL3 deletion revealed both nonrenin-angiotensin system and renin-angiotensin system components to the development of hypertension. Increased ANG II-induced vasoconstriction was observed in mesenteric and basilar arteries in S-CUL3KO mice. Freshly isolated smooth muscle cells from S-CUL3KO exhibited an excessive cytosolic calcium concentration flux in response to ANG II. Gene expression studies of carotid arteries from S-CUL3KO mice led us to hypothesize a potential role for TRPC6 (Transient Receptor Potential Cation Channel Subfamily C Member 6) in ANG II hyperresponsiveness. TRPC6 pharmacological inhibition blunted the exaggerated ANG II-induced cytosolic calcium concentration flux in smooth muscle cells, blunted ANG II-induced vasoconstriction and lowered blood pressure in S-CUL3KO mice.</p><p><strong>Conclusions: </strong>Collectively, these data are consistent with the conclusion that loss of CUL3 function enhances ANG II sensitivity by increasing TRPC6-mediated cytosolic calcium concentration flux in smooth muscle cells.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"1208-1220"},"PeriodicalIF":6.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex Differences in BP From an Automated Oscillometric Compared With Manual Device.","authors":"Tan V Bui,James E Sharman,Niamh Chapman,Martin G Schultz,Jennifer S Ringrose,Seana L Gall,Tomas L Bothe,Tammy M Brady,Dean S Picone","doi":"10.1161/hypertensionaha.124.24640","DOIUrl":"https://doi.org/10.1161/hypertensionaha.124.24640","url":null,"abstract":"BACKGROUNDAutomated blood pressure (BP) devices may be less accurate in women than men, but this requires further investigation. This study aimed to determine sex differences in automated BP, measured with a single brand and model of device, compared with manual BP, with a focus on cuff sizes and associations with measures of adiposity.METHODSAutomated (Omron HEM-907XL) and manual BP were taken sequentially in a random order among a subsample of participants attending the US National Health and Nutrition Examination Survey, 2017 to 2018. Anthropometry and dual-energy x-ray absorptiometry were used to record body size and composition. Analyses, including multivariable regression to determine sex differences in BP, by cuff size, followed complex survey statistical principles.RESULTSA total of 3735 participants (49.0% women [95% CI, 46.4-51.6], 45 years [43-46]) were included. In women, automated systolic BP (SBP) incrementally underestimated manual SBP across larger cuffs up to extra-large (-6.4 mm Hg [-8.0 to -4.9]). In men, automated SBP underestimated manual SBP only with extra-large cuffs (-2.4 mm Hg [95% CI-3.9 to -0.9]). Underestimation by automated SBP with extra-large cuffs was independently associated with all measures of body size indicative of increased adiposity in both women and men. Hypertension classification from automated and manual SBP had moderate agreement for adult/large cuffs (weighted kappa range 0.66-0.79) but weak agreement for extra-large cuffs (0.55-0.58) for women and men.CONCLUSIONSThe automated device used in this study underestimated manual SBP at larger cuff sizes, which was associated with indices of adiposity. Poorer accuracy of automated BP in larger cuff sizes could contribute to inequitable BP-related health care for women and men and requires further investigation.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"637 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144521341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Analyses to Identify the Roles of <i>GPX1</i> in Frailty and Hypertension.","authors":"Bang-Bang Huang, Qin Liu, Xing Yu, Yi-Jun Chen, Ye-Bei Liang, Ming-Zhong Yu, Yi-Fei Qiu, Fei-Yun Zhang, Jing-Xin Wang, Shi-Hui Fu, Liang-Di Xie, Li Luo, Yu-Jie Zhang","doi":"10.1161/HYPERTENSIONAHA.125.24664","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.125.24664","url":null,"abstract":"<p><strong>Background: </strong>With aging, frailty and hypertension become increasingly prevalent comorbidities in the older population. Therefore, the aim of the study is to identify effective druggable targets for these conditions.</p><p><strong>Methods: </strong>We performed a 2-sample Mendelian randomization analysis to assess the causal effects of 2532 druggable genes on frailty, hypertension, systolic blood pressure and diastolic blood pressure. RNA expression profiling data and single-cell RNA sequencing were performed for validation. Mediation Mendelian randomization analysis was conducted to identify possible mediators participating in the effects of target genes on outcomes. Molecular docking was used to identify potential drugs.</p><p><strong>Results: </strong>After screening, the expression of Glutathione peroxidase 1 (<i>GPX1</i>) in whole blood was found to positively correlate with hypertension (β, 0.308 [95% CI, 0.266-0.349]; <i>P</i>=3.40×10^-48) and frailty index (β, 0.172 [95% CI, 0.141-0.204]; <i>P</i>=1.21×10^-26), which was validated by RNA expression profiling data. Mediation Mendelian randomization analysis indicated that glycine and carnitine/ergothioneine mediated the effects of <i>GPX1</i> on hypertension and frailty. Single-cell RNA sequencing further validated the mediating effects of glycine metabolism and carnitine transport at the cellular level. Moreover, <i>GPX1</i> expression in mononuclear phagocytes was associated with upregulated inflammatory responses and immune activation. Molecular docking analysis identified biochanin A and epigallocatechin gallate as potential agents for <i>GPX1</i> with high affinity.</p><p><strong>Conclusions: </strong>Collectively, <i>GPX1</i> is a potential therapeutic target for mitigating both frailty and hypertension.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Analyses to Identify the Roles of GPX1 in Frailty and Hypertension.","authors":"Bang-Bang Huang,Qin Liu,Xing Yu,Yi-Jun Chen,Ye-Bei Liang,Ming-Zhong Yu,Yi-Fei Qiu,Fei-Yun Zhang,Jing-Xin Wang,Shi-Hui Fu,Liang-Di Xie,Li Luo,Yu-Jie Zhang","doi":"10.1161/hypertensionaha.125.24664","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.24664","url":null,"abstract":"BACKGROUNDWith aging, frailty and hypertension become increasingly prevalent comorbidities in the older population. Therefore, the aim of the study is to identify effective druggable targets for these conditions.METHODSWe performed a 2-sample Mendelian randomization analysis to assess the causal effects of 2532 druggable genes on frailty, hypertension, systolic blood pressure and diastolic blood pressure. RNA expression profiling data and single-cell RNA sequencing were performed for validation. Mediation Mendelian randomization analysis was conducted to identify possible mediators participating in the effects of target genes on outcomes. Molecular docking was used to identify potential drugs.RESULTSAfter screening, the expression of Glutathione peroxidase 1 (GPX1) in whole blood was found to positively correlate with hypertension (β, 0.308 [95% CI, 0.266-0.349]; P=3.40×10-48) and frailty index (β, 0.172 [95% CI, 0.141-0.204]; P=1.21×10-26), which was validated by RNA expression profiling data. Mediation Mendelian randomization analysis indicated that glycine and carnitine/ergothioneine mediated the effects of GPX1 on hypertension and frailty. Single-cell RNA sequencing further validated the mediating effects of glycine metabolism and carnitine transport at the cellular level. Moreover, GPX1 expression in mononuclear phagocytes was associated with upregulated inflammatory responses and immune activation. Molecular docking analysis identified biochanin A and epigallocatechin gallate as potential agents for GPX1 with high affinity.CONCLUSIONSCollectively, GPX1 is a potential therapeutic target for mitigating both frailty and hypertension.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"67 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benefit and Harm of Intensive Blood Pressure Control by Cardiovascular Risk.","authors":"Xilan Dong,Qianhui Ling,Xueyan Zhao,Qirui Song,Jun Cai","doi":"10.1161/hypertensionaha.125.25162","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.25162","url":null,"abstract":"BACKGROUNDCurrent guidelines for blood pressure treatment are stratified by cardiovascular disease (CVD) risk levels. However, the impact of CVD risk on the benefits and harms of intensive blood pressure control remains unknown. This study aims to evaluate the cardiovascular benefits and treatment-related adverse events associated with intensive blood pressure control across different CVD risk levels.METHODSFrom the STEP trial (Strategy of Blood Pressure Intervention in Older Hypertensive Patients), 8262 patients were stratified by tertiles of baseline 10-year CVD risk. Benefit and harm were determined as a reduction of primary outcomes and an increase of adverse events, respectively. Cox proportional hazard models were used to examine the association between CVD risk and outcome events in each tertile. The Poisson regression model was used to predict the benefits and harms.RESULTSDuring a median follow-up of 3.32 years, 333 primary outcomes and 611 adverse events occurred. Within each risk tertile, there were lower rates of the primary outcome in the intensive treatment group (overall hazard ratio, 0.76 [95% CI, 0.61-0.94]), and the hazard ratio for adverse events was 1.1 (95% CI, 0.94-1.28). Patients with higher CVD risk had higher absolute risk reduction of the primary outcome and absolute risk increase of adverse events. The predicted benefit-to-harm ratio differed significantly across each CVD risk tertile but favored intensive control overall.CONCLUSIONSHigher CVD risk was associated with increased benefit and harm from intensive blood pressure control. Although benefit and harm profiles varied across CVD risk levels, the overall benefit was greater than harm in all risk tertiles.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"17 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac Sympathetic Nerve Activity Is Not Elevated in Ovine Hypertensive HFpEF.","authors":"Joshua W-H Chang,Bindu George,Mridula Pachen,Julia Shanks,Rohit Ramchandra","doi":"10.1161/hypertensionaha.125.24884","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.24884","url":null,"abstract":"BACKGROUNDThe sympathetic nervous system is a crucial mediator of cardiovascular variables during exercise. However, its role in heart failure with preserved ejection fraction (HFpEF), where exercise intolerance is a cardinal feature, is poorly understood. Currently, there is scant and no clear evidence of heightened cardiac sympathetic nerve activity (CSNA) in HFpEF, which might explain why β-blockers lack convincing prognostic benefit in this syndrome. Accordingly, we utilized gold standard direct recordings to test the hypothesis that resting levels of CSNA are not elevated in HFpEF. We also tested whether β-blockers in HFpEF cause further impairments in the hemodynamic determinants of exercise capacity.METHODSExperiments were conducted in a conscious large animal (ovine) model of hypertensive HFpEF that exhibits similarly impaired exercise hemodynamics as patients with HFpEF. Direct recordings of CSNA were made in this model and compared with non-HFpEF sheep. In addition, hemodynamic responses to graded treadmill exercise testing were compared before and after β-blocker administration.RESULTSGold standard direct recordings of resting CSNA were not elevated in HFpEF sheep. Inhibition of this activity using a β-blocker further impaired exercise hemodynamics (cardiac output, heart rate and pulmonary capillary wedge pressure) in HFpEF sheep. In addition, non-HFpEF and HFpEF sheep exhibited differential exercise hemodynamic responses to β-blockers.CONCLUSIONSOur data demonstrates that CSNA is not elevated in an ovine model of hypertensive HFpEF and suggests that favorable exercise hemodynamics in HFpEF are reliant upon β-adrenergic activation. Our findings provide a mechanistic rationale for why β-blockers should be avoided in patients with HFpEF.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"17 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}