Hypertension最新文献

{"title":"Transforming Hypertension Diagnosis and Management in The Era of Artificial Intelligence: A 2023 National Heart, Lung, and Blood Institute (NHLBI) Workshop Report.","authors":"Daichi Shimbo, Rashmee U Shah, Marwah Abdalla, Ritu Agarwal, Faraz S Ahmad, Gabriel Anaya, Zachi I Attia, Sheana Bull, Alexander R Chang, Yvonne Commodore-Mensah, Keith Ferdinand, Kensaku Kawamoto, Rohan Khera, Jane Leopold, James Luo, Sonya Makhni, Bobak J Mortazavi, Young S Oh, Lucia C Savage, Erica S Spatz, George Stergiou, Mintu P Turakhia, Paul K Whelton, Clyde W Yancy, Erin Iturriaga","doi":"10.1161/HYPERTENSIONAHA.124.22095","DOIUrl":"10.1161/HYPERTENSIONAHA.124.22095","url":null,"abstract":"<p><p>Hypertension is among the most important risk factors for cardiovascular disease, chronic kidney disease, and dementia. The artificial intelligence (AI) field is advancing quickly, and there has been little discussion on how AI could be leveraged for improving the diagnosis and management of hypertension. AI technologies, including machine learning tools, could alter the way we diagnose and manage hypertension, with potential impacts for improving individual and population health. The development of successful AI tools in public health and health care systems requires diverse types of expertise with collaborative relationships between clinicians, engineers, and data scientists. Unbiased data sources, management, and analyses remain a foundational challenge. From a diagnostic standpoint, machine learning tools may improve the measurement of blood pressure and be useful in the prediction of incident hypertension. To advance the management of hypertension, machine learning tools may be useful to find personalized treatments for patients using analytics to predict response to antihypertension medications and the risk for hypertension-related complications. However, there are real-world implementation challenges to using AI tools in hypertension. Herein, we summarize key findings from a diverse group of stakeholders who participated in a workshop held by the National Heart, Lung, and Blood Institute in March 2023. Workshop participants presented information on communication gaps between clinical medicine, data science, and engineering in health care; novel approaches to estimating BP, hypertension risk, and BP control; and real-world implementation challenges and issues.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"36-45"},"PeriodicalIF":6.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619872","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":"Mechanistic Insights Into Redox Damage of the Podocyte in Hypertension.","authors":"Daria V Ilatovskaya, Amanda Behr, Alexander Staruschenko, Gentzon Hall, Oleg Palygin","doi":"10.1161/HYPERTENSIONAHA.124.22068","DOIUrl":"10.1161/HYPERTENSIONAHA.124.22068","url":null,"abstract":"<p><p>Podocytes are specialized cells within the glomerular filtration barrier, which are crucial for maintaining glomerular structural integrity and convective ultrafiltration. Podocytes exhibit a unique arborized morphology with foot processes interfacing by slit diaphragms, ladder-like, multimolecular sieves, which provide size and charge selectivity for ultrafiltration and transmembrane signaling. Podocyte dysfunction, resulting from oxidative stress, dysregulated prosurvival signaling, or structural damage, can drive the development of proteinuria and glomerulosclerosis in hypertensive nephropathy. Functionally, podocyte injury leads to actin cytoskeleton rearrangements, foot process effacement, dysregulated slit diaphragm protein expression, and impaired ultrafiltration. Notably, the renin-angiotensin system plays a pivotal role in podocyte function, with beneficial AT2R (angiotensin receptor 2)-mediated nitric oxide (NO) signaling to counteract AT1R (angiotensin receptor 1)-driven calcium (Ca²⁺) influx and oxidative stress. Disruption of this balance contributes significantly to podocyte dysfunction and drives albuminuria, a marker of kidney damage and overall disease progression. Oxidative stress can also lead to sustained ion channel-mediated Ca²⁺ influx and precipitate cytoskeletal disorganization. The complex interplay between GPCR (G-protein coupled receptor) signaling, ion channel activation, and redox injury pathways underscores the need for additional research aimed at identifying targeted therapies to protect podocytes and preserve glomerular function. Earlier detection of albuminuria and podocyte injury through routine noninvasive diagnostics will also be critical in populations at the highest risk for the development of hypertensive kidney disease. In this review, we highlight the established mechanisms of oxidative stress-mediated podocyte damage in proteinuric kidney diseases, with an emphasis on a hypertensive renal injury. We will also consider emerging therapies that have the potential to selectively protect podocytes from redox-related injury.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"14-25"},"PeriodicalIF":6.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619264","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":"Increased TRPV4 Channel Expression Enhances and Impairs Blood Vessel Function in Hypertension.","authors":"Xun Zhang, Charlotte Buckley, Matthew D Lee, Christine Salaun, Margaret MacDonald, Calum Wilson, John G McCarron","doi":"10.1161/HYPERTENSIONAHA.124.23092","DOIUrl":"10.1161/HYPERTENSIONAHA.124.23092","url":null,"abstract":"<p><strong>Background: </strong>Endothelial cell TRPV4 (transient receptor potential vanilloid 4) channels provide a control point that is pivotal in regulating blood vessel diameter by mediating the Ca²⁺-dependent release of endothelial-derived vasoactive factors. In hypertension, TRPV4-mediated control of vascular function is disrupted, but the underlying mechanisms and precise physiological consequences remain controversial.</p><p><strong>Methods: </strong>Here, using a comprehensive array of methodologies, endothelial TRPV4 channel function was examined in intact mesenteric resistance arteries from normotensive Wistar-Kyoto and spontaneously hypertensive rats.</p><p><strong>Results: </strong>Our results show there is a notable shift in vascular reactivity in hypertension characterized by enhanced endothelium-dependent vasodilation at low levels of TRPV4 channel activation. However, at higher levels of TRPV4 activity, this vasodilatory response is reversed, contributing to the aberrant vascular tone observed in hypertension. The change in response, from dilation to constriction, was accompanied by a shift in intracellular Ca²⁺ signaling modalities arising from TRPV4 activity. Oscillatory TRPV4-evoked IP₃ (inositol triphosphate)-mediated Ca²⁺ release, which underlies dilation, decreased, while the contraction inducing sustained Ca²⁺ rise, arising from TRPV4-mediated Ca²⁺ influx, increased. Our findings also reveal that while the sensitivity of endothelial cell TRPV4 to activation was unchanged, expression of the channel is upregulated and IP₃ receptors are downregulated in hypertension.</p><p><strong>Conclusions: </strong>These data highlight the intricate interplay between endothelial TRPV4 channel expression, intracellular Ca²⁺ signaling dynamics, and vascular reactivity. Moreover, the data support a new unifying hypothesis for the vascular impairment that accompanies hypertension. Specifically, endothelial cell TRPV4 channels play a dual role in modulating blood vessel function in hypertension.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"57-68"},"PeriodicalIF":6.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11654454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499404","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":"Genetics of Hypertension: Additive and Interactive Effects.","authors":"Zdenka Pausova, Johanne Tremblay, Pavel Hamet","doi":"10.1161/HYPERTENSIONAHA.124.21724","DOIUrl":"10.1161/HYPERTENSIONAHA.124.21724","url":null,"abstract":"","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"3-7"},"PeriodicalIF":6.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619258","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":"Response of Blood Pressure to Renal Denervation Is Not Associated With Genetic Variants.","authors":"Christian Delles, Roland E Schmieder, Rónán Daly, Dennis Kannenkeril, Agnes Bosch, Lucas Lauder, Michael Kunz, Michael Böhm, Graham Hamilton, Raphael S Schmieder, Axel Schmid, Pawel Herzyk, Felix Mahfoud","doi":"10.1161/HYPERTENSIONAHA.124.23393","DOIUrl":"10.1161/HYPERTENSIONAHA.124.23393","url":null,"abstract":"<p><strong>Background: </strong>Renal denervation lowers blood pressure (BP) in patients with uncontrolled hypertension. We conducted an unbiased genomic screen to identify genetic variants that may associate with BP response to renal denervation (RDN).</p><p><strong>Methods: </strong>Patients (n=268) with uncontrolled resistant hypertension (baseline BP, 166±21/90±15 mm Hg) who underwent endovascular RDN using the Symplicity catheter (Medtronic, Inc, Santa Rosa, CA) were included. Reduction in 24-hour ambulatory systolic BP was assessed at 6 months and divided into 2 groups: above and below the median response of 6.0 mm Hg, taking preintervention 24-hour ambulatory BP and regression to the mean into account. Whole exome sequencing assessing 249 669 variants, was conducted using Illumina NovaSeq technology read on a NovaSeq S4 Flow Cell device.</p><p><strong>Results: </strong>We did not identify individual gene variants associated with BP response following RDN. These findings were confirmed after adjustment for sex and in a sensitivity analysis looking at tertiles of BP response. We also explored specific variants in <i>AGT</i>, <i>ADD1</i>, ADRB1, <i>ADRB2</i>, and <i>SCNN1A</i> that have been proposed as potential candidate genes for response and found no association (all <i>P</i>>0.13). Gene ontology analysis of variants across the 2 responder groups highlighted differences in biologic processes such as cell adhesion and molecular function such as protein tyrosine kinase activity.</p><p><strong>Conclusions: </strong>The response to RDN, in terms of 24-hour BP reduction, was not associated with the genetic profile of patients with resistant hypertension. These data do not support the use of a genetic score to identify potential responders to RDN.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"118-125"},"PeriodicalIF":6.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11654447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681735","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":"Evolutionary Characteristics in Primary Aldosteronism Patients.","authors":"Yinjie Gao, Yu Wang, Yue Zhou, Xiaoyan Chang, Yushi Zhang, Min Nie, Anli Tong","doi":"10.1161/HYPERTENSIONAHA.124.23398","DOIUrl":"10.1161/HYPERTENSIONAHA.124.23398","url":null,"abstract":"<p><strong>Background: </strong>Primary aldosteronism is predominantly caused by excessive aldosterone production from the adrenal cortex, and the aldosterone-producing structures could take many forms, like adenomas, nodules, micronodules, and so on. Most studies of primary aldosteronism were limited to the hotspot driver genes responsible for autonomous aldosterone production; however, the panoramic genetic architecture and genomic alterations of aldosterone-producing structures and their adjacent hyperplasia glands remain unknown.</p><p><strong>Methods: </strong>In this study, whole-exome sequencing and transcriptome sequencing (RNA-seq) analyses were performed using functional nodules and matched hyperplasia tissues, which were microdissected guided by aldosterone synthase immunohistochemistry. Phylogenetic trees were constructed based on the shared and unique mutations, gene mutation spectrums, and clonal characteristics.</p><p><strong>Results: </strong>The rates of mutations represented higher means of functional nodules than hyperplasia samples, and the little mutational overlap was shown between the 2 groups on phylogenetic trees. The mutations of the aldosterone driver gene (<i>KCNJ5</i> or <i>CACNA1D</i>) were only observed in functional nodules and indicated almost the largest values of cancer cell fraction. Moreover, the functional nodules also harbored some potential variants related to cell proliferation, which were not detected in hyperplasia tissues. Transcriptome analysis suggested that only 25.5% upregulated and 23.3% downregulated genes overlapped between functional nodules and hyperplasia tissues.</p><p><strong>Conclusions: </strong>This study demonstrated a genetic and transcriptome landscape of aldosterone-producing structures and adjacent hyperplasia glands in primary aldosteronism. The results indicated independent clonal origins on functional nodules and hyperplasia tissues, and little mutual evolutionary relationship was found on their phylogenetic trees.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"96-105"},"PeriodicalIF":6.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582556","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":"Home Blood Pressure Measurements Are Not Performed According to Guidelines and Standardized Education Is Urgently Needed.","authors":"Eleanor Clapham, Dean S Picone, Samuel Carmichael, George S Stergiou, Norm R C Campbell, John Stevens, Carol Batt, Aletta E Schutte, Niamh Chapman","doi":"10.1161/HYPERTENSIONAHA.124.23678","DOIUrl":"10.1161/HYPERTENSIONAHA.124.23678","url":null,"abstract":"<p><strong>Background: </strong>Patient education is needed to perform home blood pressure measurement (HBPM) according to blood pressure (BP) guidelines. It is not known how BP is measured at home and what education is provided, which was the aim of the study.</p><p><strong>Methods: </strong>Mixed-methods study among Australian adults who perform HBPM (June to December 2023). Participants completed a 30-item online survey on whether they followed guideline recommendations and the education they received for HBPM. Phone interviews were conducted among a purposive sample to further explore survey topics.</p><p><strong>Results: </strong>Participants (n=350) were middle-aged (58±16 years; 54% women), and most (n=250, 71%) had hypertension. Guideline recommendations for HBPM were not always followed by survey participants. Most participants measured BP seated (n=316, 90%) with the cuff fitted to a bare arm (n=269, 77%). Only 15% measured BP in the morning and evening (n=54) and 26% averaged the BP readings over 7 days (n=90). Interview participants (n=34) described measuring BP at \"different times of the day after doing different things.\" One-third of participants (n=112, 37%) received education for HBPM, which interview participants described as vague verbal instructions from health care practitioners. Participants who received education did not perform high-quality HBPM. Participants who did not receive education mimicked BP measurement methods of health care practitioners, \"I do it the way I've seen them do it.\"</p><p><strong>Conclusions: </strong>HBPM is not performed according to guideline recommendations, and adults who received ad hoc education did not perform high-quality HBPM. These findings highlight a need for effective education to support HBPM for clinical decision-making.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"149-159"},"PeriodicalIF":6.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710029","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":"Clinical Correlates of Efficacy of Pyridostigmine in the Treatment of Orthostatic Hypotension.","authors":"Luis E Okamoto,Emily Walsh,Andre Diedrich,Cyndya A Shibao,Alfredo Gamboa,Bonnie K Black,Sachin Paranjape,James A S Muldowney,Ralf Habermann,Amanda Peltier,Kishan Tarpara,Italo Biaggioni","doi":"10.1161/hypertensionaha.124.24050","DOIUrl":"https://doi.org/10.1161/hypertensionaha.124.24050","url":null,"abstract":"BACKGROUNDThe cholinesterase inhibitor pyridostigmine is used to treat orthostatic hypotension by facilitating cholinergic neurotransmission in autonomic ganglia, thereby harnessing residual sympathetic tone to increase blood pressure (BP) preferentially in the upright posture. We hypothesized that less severe autonomic impairment was associated with greater pressor responses to pyridostigmine.METHODSTo identify predictors of pressor response, linear regression analyses between the effect of pyridostigmine on upright BP and markers of autonomic impairment were retrospectively conducted on 38 patients who had a medication trial with pyridostigmine (60 mg single dose).RESULTSPyridostigmine increased upright BP by 4±2/3±2 mm Hg but with a wide range of responses (-20/-15 to 29/27 mm Hg; interquartile range, -6/-4 to 11/8 mm Hg). No differences were found between multiple system atrophy (n=14) and patients with pure autonomic failure (n=24). The upright BP response to pyridostigmine was negatively correlated with supine BP and with the pressure recovery time of the Valsalva maneuver, an index of severity of autonomic impairment. In patients with multiple system atrophy, the systolic blood pressure pressor response to pyridostigmine was also positively correlated with the increase in upright heart rate divided by the fall in systolic blood pressure (∆ heart rate/∆ systolic blood pressure) and with upright plasma norepinephrine, both surrogates of residual autonomic function.CONCLUSIONSPatients with less severe autonomic impairment are more likely to have a positive pressor response to pyridostigmine. Importantly, in this cohort of patients with severe autonomic failure, pyridostigmine was not effective in those with supine hypertension who would benefit the most from the preferential pressor effect of the drug on upright BP.REGISTRATIONURL: http://www.clinicaltrials.gov; Unique identifier: NCT00223691.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"14 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887585","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":"Genetic Variants Associated With Preeclampsia and Maternal Serum sFLT1 Levels.","authors":"Jasmine A Mack,Ulla Sovio,Felix R Day,Francesca Gaccioli,Emma Cook,Nadua Bayzid,Marius Cotic,Nathan Dunton,Gaganjit Madhan,Alison Motsinger-Reif,John R B Perry,D Stephen Charnock-Jones,Gordon C S Smith","doi":"10.1161/hypertensionaha.124.23400","DOIUrl":"https://doi.org/10.1161/hypertensionaha.124.23400","url":null,"abstract":"BACKGROUNDElevated maternal serum sFLT1 (soluble fms-like tyrosine kinase 1) has a key role in the pathophysiology of preeclampsia. We sought to determine the relationship between the maternal and fetal genome and maternal levels of sFLT1 at 12, 20, 28, and 36 weeks of gestational age (wkGA).METHODSWe studied a prospective cohort of nulliparous women (3968 mother-child pairs). We related maternal and fetal genotype to the adjusted sFLT1 Z score and sFLT1:placental growth factor (PlGF) ratio Z score at each wkGA and the change in the Z score between 28 and 36 wkGA (Δ36-28). We studied genetic variants from a previous fetal genome-wide association study of preeclampsia and an externally defined polygenic score from a maternal genome-wide association study of preeclampsia.RESULTSFour variants from the fetal preeclampsia genome-wide association study were positively associated with sFLT1 and sFLT1:PlGF Z score at 36 wkGA, and FLT1 enhancer single-nucleotide polymorphisms were associated with increased Δ36-28 of sFLT1. The associations were specific for the fetal genome or stronger for the fetal than the maternal genome. An increased risk of preeclampsia based on the maternal polygenic score for preeclampsia was associated with lower levels of sFLT1 and sFLT1:PlGF ratio in the first trimester and a greater Δ36-28 for sFLT1.CONCLUSIONSThe current data are consistent with a causal association between sFLT1 released by the placenta in late pregnancy and the pathophysiology of preeclampsia. The data are also consistent with maternal components to the protective effect of high sFLT1 in the first trimester and the rise in third-trimester sFLT1 levels and preeclampsia.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"54 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887577","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":"Reduced AT2R Signaling Contributes to Endothelial Dysfunction After Preeclampsia.","authors":"Kelsey S Schwartz,Mingyao Sun,Diana I Jalal,Mark K Santillan,Anna E Stanhewicz","doi":"10.1161/hypertensionaha.124.24098","DOIUrl":"https://doi.org/10.1161/hypertensionaha.124.24098","url":null,"abstract":"BACKGROUNDWomen who had preeclampsia (a history of preeclampsia) have a >4-fold risk of developing cardiovascular disease compared with women who had an uncomplicated pregnancy (history of healthy pregnancy). Despite the remission of clinical symptoms after pregnancy, vascular endothelial dysfunction persists postpartum, mediated in part by exaggerated Ang II (angiotensin II)-mediated constriction. However, the role of vasodilatory AT2Rs (Ang II type 2 receptors) in this dysfunction is unknown. We examined the functional role of AT2R in the microvasculature postpartum and whether acute activation of AT2R improves microvascular endothelial function after preeclampsia.METHODSOverall, 24 women (n=12/group) participated. We measured cutaneous vascular conductance responses to (1) graded infusion of compound 21 (AT2R agonist; 10-14-10-8M) alone or with NG-nitro-l-arginine methyl ester (NO synthase inhibitor; 15 mM) and (2) a standardized local heating protocol in control and 10-11M compound 21-treated sites. Expression of Ang II receptor subtypes I and II in biopsied venous endothelial cells was quantified using immunofluorescence.RESULTSAT2R-mediated dilation (P<0.01) and the NO-dependent contribution (P=0.003) of this response were reduced in women with a history of preeclampsia. Endothelial AT2R expression was lower in women with a history of preeclampsia (P<0.01), but there were no differences in endothelial AT1R (Ang II type 1 receptor) expression (P>0.05). Acute activation of AT2R during local heating improved endothelium (P<0.01) and NO-dependent (P<0.01) dilation in women with a history of preeclampsia but had no effect in women with a history of healthy pregnancy (both P>0.05).CONCLUSIONSReductions in AT2R-mediated dilation contribute to attenuated or impaired endothelial function in women who had a pregnancy complicated by preeclampsia. Furthermore, AT2R activation may improve endothelial function through NO-dependent mechanisms in otherwise healthy women who had preeclampsia before the onset of cardiovascular disease.REGISTRATIONURL: https://www.clinicaltrials.gov; Unique identifier: NCT05937841.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"202 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887595","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}