{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T04:39:24Z","timestamp":1792471164364,"version":"4.5.0"},"reference-count":64,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100019603","name":"Faculty of Medicine, American University of Beirut","doi-asserted-by":"publisher","award":["AUB\u2010MPP #320148"],"award-info":[{"award-number":["AUB\u2010MPP #320148"]}],"id":[{"id":"10.13039\/100019603","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp;amp; Metabol"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Prediabetes is increasingly recognised as a stage at which cardiovascular and renal dysfunction begin to develop despite the absence of overt metabolic disease. The mechanisms underlying these early alterations remain poorly understood. Because adipose tissues surrounding blood vessels and kidneys can locally generate components of the renin\u2013angiotensin system (RAS), we hypothesised that subclinical RAS activation contributes to early cardiorenal dysfunction in prediabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using a pre\u2010established normotensive, non\u2010obese rat model of prediabetes induced by 12\u2009weeks of mild hypercaloric feeding, we examined the impact of systemic angiotensin II (AngII) elevation and angiotensin\u2010converting enzyme (ACE) inhibition on cardio\u2010, cerebro\u2010 and renovascular function by invasive hemodynamics, ex\u00a0vivo pressure myography, and ex\u00a0vivo renal perfusion experiments, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Prediabetic rats exhibited impaired parasympathetic baroreceptor sensitivity and altered renovascular endothelium\u2010dependent vasodilation despite preserved blood pressure and cardiac function. Systemic AngII infusion further exacerbated autonomic and renovascular dysfunction. In contrast, treatment with a non\u2010hypotensive dose of the ACE inhibitor captopril restored baroreceptor sensitivity, improved renovascular endothelial function, reduced brainstem inflammation, and attenuated renal tubular fibrosis. Examination of perivascular and perirenal adipose tissues revealed significantly higher protein concentration of ACE1 in prediabetic rats compared to controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings are consistent with an early activation of RAS contributing to subclinical cardiovascular and renal dysfunction during prediabetes independently of hypertension. Targeting RAS signalling at this early stage may therefore represent a strategy to limit progression of cardiorenal complications along the continuum from prediabetes to diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/edm2.70363","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T04:03:52Z","timestamp":1792469032000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Renin\u2013Angiotensin System Activation Drives Early Cardiorenal Dysfunction in Normotensive Prediabetes"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6403-9348","authenticated-orcid":false,"given":"Nour\u2010Mounira Z.","family":"Bakkar","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine American University of Beirut  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana","family":"Ghazi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine American University of Beirut  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahed","family":"Mougharbil","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine American University of Beirut  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9418-4071","authenticated-orcid":false,"given":"Safaa H.","family":"Hammoud","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics Beirut Arab University  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramzi","family":"Sabra","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine American University of Beirut  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3004-5675","authenticated-orcid":false,"given":"Ali H.","family":"Eid","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, QU Health Qatar University  Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3432-3038","authenticated-orcid":false,"given":"Ahmed F.","family":"El\u2010Yazbi","sequence":"additional","affiliation":[{"name":"Research and Innovation Hub Alamein International University  Alamein Egypt"},{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Alexandria University  Alexandria Egypt"},{"name":"Department of Chemistry and Biochemistry Texas Tech University  Lubbock Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/s41569-023-00877-z","article-title":"Cardiovascular Risk in Diabetes Mellitus: Epidemiology, Assessment and Prevention","volume":"20","author":"Wong N. D.","year":"2023","journal-title":"Nature Reviews Cardiology"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S2213-8587(16)30010-9","article-title":"The Changing Face of Diabetes Complications","volume":"4","author":"Gregg E. W.","year":"2016","journal-title":"Lancet Diabetes & Endocrinology"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/j.tips.2011.07.006","article-title":"The Renin\u2013Angiotensin\u2013Aldosterone System and Glucose Homeostasis","volume":"32","author":"Luther J. M.","year":"2011","journal-title":"Trends in Pharmacological Sciences"},{"key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1152\/physrev.00038.2017","article-title":"Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology","volume":"98","author":"Forrester S. J.","year":"2018","journal-title":"Physiological Reviews"},{"key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1016\/j.jacc.2009.10.060","article-title":"Pre\u2010Diabetes and the Risk for Cardiovascular Disease: A Systematic Review of the Evidence","volume":"55","author":"Ford E. S.","year":"2010","journal-title":"Journal of the American College of Cardiology"},{"key":"e_1_2_10_7_1","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.m2297","article-title":"Association Between Prediabetes and Risk of All Cause Mortality and Cardiovascular Disease: Updated Meta\u2010Analysis","volume":"370","author":"Cai X.","year":"2020","journal-title":"BMJ"},{"key":"e_1_2_10_8_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.atherosclerosis.2018.09.004","article-title":"Prediabetes and Cardiovascular Disease Risk: A Nested Case\u2010Control Study","volume":"278","author":"Hu H.","year":"2018","journal-title":"Atherosclerosis"},{"key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"440","DOI":"10.2337\/dc19-1683","article-title":"Glycated Hemoglobin, Prediabetes, and the Links to Cardiovascular Disease: Data From UK Biobank","volume":"43","author":"Welsh C.","year":"2020","journal-title":"Diabetes Care"},{"key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/S2213-8587(23)00086-4","article-title":"Metabolic Health and Cardiometabolic Risk Clusters: Implications for Prediction, Prevention, and Treatment","volume":"11","author":"Stefan N.","year":"2023","journal-title":"Lancet Diabetes & Endocrinology"},{"key":"e_1_2_10_11_1","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s44324-024-00036-z","article-title":"Human Adipose Depots' Diverse Functions and Dysregulations During Cardiometabolic Disease","volume":"2","author":"Ziegler A. K.","year":"2024","journal-title":"NPJ Metabolic Health and Disease"},{"key":"e_1_2_10_12_1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0091-7435(87)90087-9","article-title":"Incidence and Precursors of Hypertension in Young Adults: The Framingham Offspring Study","volume":"16","author":"Garrison R. J.","year":"1987","journal-title":"Preventive Medicine"},{"key":"e_1_2_10_13_1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1291\/hypres.18.181","article-title":"Framingham Study Insights Into Hypertensive Risk of Cardiovascular Disease","volume":"18","author":"Kannel W. B.","year":"1995","journal-title":"Hypertension Research"},{"key":"e_1_2_10_14_1","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1001\/archinte.162.16.1867","article-title":"Overweight and Obesity as Determinants of Cardiovascular Risk: The Framingham Experience","volume":"162","author":"Wilson P. W.","year":"2002","journal-title":"Archives of Internal Medicine"},{"key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1007\/s11906-004-0083-8","article-title":"The Tissue Renin\u2010Angiotensin\u2010Aldosterone System in Diabetes Mellitus","volume":"6","author":"Hanes D. S.","year":"2004","journal-title":"Current Hypertension Reports"},{"key":"e_1_2_10_16_1","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1161\/01.HYP.23.2.258","article-title":"Tissue Angiotensin Converting Enzyme in Cardiac and Vascular Hypertrophy, Repair, and Remodeling","volume":"23","author":"Johnston C. I.","year":"1994","journal-title":"Hypertension"},{"key":"e_1_2_10_17_1","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.atherosclerosis.2006.12.036","article-title":"High Dose Treatment With Angiotensin II Receptor Blocker in Patients With Hypertension: Differential Effect of Tissue Protection Versus Blood Pressure Lowering","volume":"197","author":"Shargorodsky M.","year":"2008","journal-title":"Atherosclerosis"},{"key":"e_1_2_10_18_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2022.115337","article-title":"Adipose Tissue Mitochondrial Dysfunction and Cardiometabolic Diseases: On the Search for Novel Molecular Targets","volume":"206","author":"AlZaim I.","year":"2022","journal-title":"Biochemical Pharmacology"},{"key":"e_1_2_10_19_1","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1042\/CS20220404","article-title":"Depot\u2010Specific Adipose Tissue Modulation by SGLT2 Inhibitors and GLP1 Agonists Mediates Their Cardioprotective Effects in Metabolic Disease","volume":"136","author":"Bakkar N.\u2010M. Z.","year":"2022","journal-title":"Clinical Science"},{"key":"e_1_2_10_20_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/978-3-031-62131-4_3","volume-title":"Oxidative Stress in Cardiovascular\u2010Metabolic Diseases","author":"Bakkar N.\u2010M. Z.","year":"2024"},{"key":"e_1_2_10_21_1","doi-asserted-by":"crossref","DOI":"10.1096\/fj.202402470R","article-title":"Targeting GSK\u20103\u03b2 for Adipose Dysfunction and Cardiovascular Complications of Metabolic Disease: An Entangled WNT\/\u03b2\u2010Catenin Question","volume":"38","author":"Alotaiq N.","year":"2024","journal-title":"FASEB Journal"},{"key":"e_1_2_10_22_1","doi-asserted-by":"crossref","DOI":"10.3389\/fcvm.2020.602088","article-title":"Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases","volume":"7","author":"AlZaim I.","year":"2020","journal-title":"Frontiers in Cardiovascular Medicine"},{"key":"e_1_2_10_23_1","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2021.707126","article-title":"Perirenal Adipose Tissue Inflammation: Novel Insights Linking Metabolic Dysfunction to Renal Diseases","volume":"12","author":"Hammoud S. H.","year":"2021","journal-title":"Frontiers in Endocrinology"},{"key":"e_1_2_10_24_1","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1042\/CS20190227","article-title":"Targeting Perivascular and Epicardial Adipose Tissue Inflammation: Therapeutic Opportunities for Cardiovascular Disease","volume":"134","author":"Rafeh R.","year":"2020","journal-title":"Clinical Science"},{"key":"e_1_2_10_25_1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1124\/molpharm.123.000704","article-title":"Thermogenic Modulation of Adipose Depots: A Perspective on Possible Therapeutic Intervention With Early Cardiorenal Complications of Metabolic Impairment","volume":"104","author":"El\u2010Yazbi A. F.","year":"2023","journal-title":"Molecular Pharmacology"},{"key":"e_1_2_10_26_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2021.105890","article-title":"The Physiologic and Physiopathologic Roles of Perivascular Adipose Tissue and Its Interactions With Blood Vessels and the Renin\u2010Angiotensin System","volume":"173","author":"Balakumar P.","year":"2021","journal-title":"Pharmacological Research"},{"key":"e_1_2_10_27_1","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/oby.2011.299","article-title":"Overproduction of Angiotensinogen From Adipose Tissue Induces Adipose Inflammation, Glucose Intolerance, and Insulin Resistance","volume":"20","author":"Kalupahana N. S.","year":"2012","journal-title":"Obesity"},{"key":"e_1_2_10_28_1","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.1161\/01.CIR.0000161954.17870.5D","article-title":"Insulin\u2010Mediated Upregulation of the Renin Angiotensin System in Human Subcutaneous Adipocytes Is Reduced by Rosiglitazone","volume":"111","author":"Harte A.","year":"2005","journal-title":"Circulation"},{"key":"e_1_2_10_29_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.xpro.2024.103276","article-title":"Protocol for Producing a Rat Model of Non\u2010Obese Prediabetes Using a Mild Hypercaloric Diet Approach","volume":"5","author":"Dwaib H. S.","year":"2024","journal-title":"STAR Protocols"},{"key":"e_1_2_10_30_1","doi-asserted-by":"crossref","DOI":"10.1155\/2018\/9389784","article-title":"Cardiac Autonomic Neuropathy as a Result of Mild Hypercaloric Challenge in Absence of Signs of Diabetes: Modulation by Antidiabetic Drugs","volume":"2018","author":"Al\u2010Assi O.","year":"2018","journal-title":"Oxidative Medicine and Cellular Longevity"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2021.114491"},{"key":"e_1_2_10_32_1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.trsl.2019.07.009","article-title":"Amelioration of Perivascular Adipose Inflammation Reverses Vascular Dysfunction in a Model of Nonobese Prediabetic Metabolic Challenge: Potential Role of Antidiabetic Drugs","volume":"214","author":"Elkhatib M. A.","year":"2019","journal-title":"Translational Research"},{"key":"e_1_2_10_33_1","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.121.023227","article-title":"Phosphorus Supplementation Mitigates Perivascular Adipose Inflammation\u2013Induced Cardiovascular Consequences in Early Metabolic Impairment","volume":"10","author":"Dwaib H. S.","year":"2021","journal-title":"Journal of the American Heart Association"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2025.117415"},{"key":"e_1_2_10_35_1","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1124\/jpet.119.262048","article-title":"Impaired Endothelium\u2010Dependent Hyperpolarization Underlies Endothelial Dysfunction During Early Metabolic Challenge: Increased ROS Generation and Possible Interference With NO Function","volume":"371","author":"Alaaeddine R.","year":"2019","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"key":"e_1_2_10_36_1","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1042\/CS20231186","article-title":"Interruption of Perivascular and Perirenal Adipose Tissue Thromboinflammation Rescues Prediabetic Cardioautonomic and Renovascular Deterioration","volume":"138","author":"Al\u2010Saidi A.","year":"2024","journal-title":"Clinical Science"},{"key":"e_1_2_10_37_1","doi-asserted-by":"crossref","first-page":"E835","DOI":"10.1152\/ajpendo.00145.2020","article-title":"Worsening Baroreflex Sensitivity on Progression to Type 2 Diabetes: Localized vs. Systemic Inflammation and Role of Antidiabetic Therapy","volume":"319","author":"Bakkar N.\u2010M. Z.","year":"2020","journal-title":"American Journal of Physiology\u2010Endocrinology and Metabolism"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.114041"},{"key":"e_1_2_10_39_1","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1002\/j.2040-4603.2017.tb00776.x","article-title":"Regulation and Functions of the Renin\u2010Angiotensin System in White and Brown Adipose Tissue","volume":"7","author":"Pahlavani M.","year":"2017","journal-title":"Comprehensive Physiology"},{"key":"e_1_2_10_40_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.cellsig.2024.111461","article-title":"Impact of the Local Renin\u2013Angiotensin System in Perivascular Adipose Tissue on Vascular Health and Disease","volume":"124","author":"Balakumar P.","year":"2024","journal-title":"Cellular Signalling"},{"key":"e_1_2_10_41_1","doi-asserted-by":"crossref","first-page":"3195","DOI":"10.1042\/CS20201099","article-title":"Renin\u2013Angiotensin System Overactivation in Perivascular Adipose Tissue Contributes to Vascular Dysfunction in Heart Failure","volume":"134","author":"Fontes M. T.","year":"2020","journal-title":"Clinical Science"},{"key":"e_1_2_10_42_1","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1161\/HYPERTENSIONAHA.112.192690","article-title":"Adipocyte Deficiency of Angiotensinogen Prevents Obesity\u2010Induced Hypertension in Male Mice","volume":"60","author":"Yiannikouris F.","year":"2012","journal-title":"Hypertension"},{"key":"e_1_2_10_43_1","doi-asserted-by":"crossref","first-page":"S53","DOI":"10.1097\/FJC.0000000000001027","article-title":"Perivascular Adipose Tissue in Vascular Function: Does Locally Synthesized Angiotensinogen Play a Role?","volume":"78","author":"Cruz\u2010L\u00f3pez E. O.","year":"2021","journal-title":"Journal of Cardiovascular Pharmacology"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2019.07.009"},{"key":"e_1_2_10_45_1","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1124\/jpet.119.262048","article-title":"Impaired Endothelium\u2010Dependent Hyperpolarization Underlies Endothelial Dysfunction During Early Metabolic Challenge: Increased ROS Generation and Possible Interference With NO Function","volume":"371","author":"Alaaeddine R.","year":"2019","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"key":"e_1_2_10_46_1","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1161\/01.HYP.35.6.1270","article-title":"Physiology and Pathophysiology of the Adipose Tissue Renin\u2010Angiotensin System","volume":"35","author":"Engeli S.","year":"2000","journal-title":"Hypertension"},{"key":"e_1_2_10_47_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.nut.2022.111862","article-title":"Obesogenic Versus Ketogenic Diets in the Regulation of the Renin\u2013Angiotensin System in Rat White and Brown Adipose Tissues","volume":"105","author":"Da Eira D.","year":"2023","journal-title":"Nutrition"},{"key":"e_1_2_10_48_1","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3109\/10641969109042063","article-title":"Influence of Perivascular Adipose Tissue on Rat Aortic Smooth Muscle Responsiveness","volume":"13","author":"Soltis E. E.","year":"1991","journal-title":"Clinical and Experimental Hypertension. Part A, Theory and Practice"},{"key":"e_1_2_10_49_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.ejphar.2010.02.006","article-title":"Mechanisms for Perivascular Adipose Tissue\u2010Mediated Potentiation of Vascular Contraction to Perivascular Neuronal Stimulation: The Role of Adipocyte\u2010Derived Angiotensin II","volume":"634","author":"Lu C.","year":"2010","journal-title":"European Journal of Pharmacology"},{"key":"e_1_2_10_50_1","article-title":"Amelioration of Cardiac Autonomic Dysfunction Mitigates Perivascular and Perirenal Adipose Inflammation and Cardiorenal Involvement in Prediabetes","volume":"36","author":"El\u2010Yazbi A. F.","year":"2022","journal-title":"FASEB Journal"},{"key":"e_1_2_10_51_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1677\/JOE-07-0284","article-title":"Comparative Expression Analysis of the Renin\u2010Angiotensin System Components Between White and Brown Perivascular Adipose Tissue","volume":"197","author":"G\u00e1lvez\u2010Prieto B.","year":"2008","journal-title":"Journal of Endocrinology"},{"key":"e_1_2_10_52_1","doi-asserted-by":"crossref","first-page":"9056","DOI":"10.1073\/pnas.0409594102","article-title":"Endothelial Dihydrofolate Reductase: Critical for Nitric Oxide Bioavailability and Role in Angiotensin II Uncoupling of Endothelial Nitric Oxide Synthase","volume":"102","author":"Chalupsky K.","year":"2005","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"e_1_2_10_53_1","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1161\/01.CIR.95.5.1115","article-title":"Role of Bradykinin in Mediating Vascular Effects of Angiotensin\u2010Converting Enzyme Inhibitors in Humans","volume":"95","author":"Hornig B.","year":"1997","journal-title":"Circulation"},{"key":"e_1_2_10_54_1","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1161\/HYPERTENSIONAHA.108.123729","article-title":"Bradykinin Protects Against Oxidative Stress\u2013Induced Endothelial Cell Senescence","volume":"53","author":"Oeseburg H.","year":"2009","journal-title":"Hypertension"},{"key":"e_1_2_10_55_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2026.179172","article-title":"Captopril Alleviates Vascular Endothelial Dysfunction by Regulating TRPV1 and Activating the eNOS Pathway","volume":"1031","author":"Lu J.","year":"2026","journal-title":"European Journal of Pharmacology"},{"key":"e_1_2_10_56_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2022.106183","article-title":"RNA Sequencing Reveals Perivascular Adipose Tissue Plasticity in Response to Angiotensin II","volume":"178","author":"Wang Z.","year":"2022","journal-title":"Pharmacological Research"},{"key":"e_1_2_10_57_1","doi-asserted-by":"crossref","first-page":"H1204","DOI":"10.1152\/ajpheart.00093.2025","article-title":"PVAT Adipocyte: Energizing, Modulating, and Structuring Vascular Function During Normotensive and Hypertensive States","volume":"328","author":"Rendon C. J.","year":"2025","journal-title":"American Journal of Physiology\u2010Heart and Circulatory Physiology"},{"key":"e_1_2_10_58_1","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1161\/HYPERTENSIONAHA.117.09512","article-title":"Perivascular Adipose Tissue Angiotensin II Type 1 Receptor Promotes Vascular Inflammation and Aneurysm Formation","volume":"70","author":"Sakaue T.","year":"2017","journal-title":"Hypertension"},{"key":"e_1_2_10_59_1","doi-asserted-by":"crossref","DOI":"10.1002\/jcp.31265","article-title":"Adipose Tissue Plasticity Mediated by the Counterregulatory Axis of the Renin\u2010Angiotensin System: Role of Mas and MrgD Receptors","volume":"239","author":"Proen\u00e7a A. B.","year":"2024","journal-title":"Journal of Cellular Physiology"},{"key":"e_1_2_10_60_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2021.120269","article-title":"Renin\u2010Angiotensin System Modulation Through Enalapril and\/or Exercise Training Improves Visceral Adiposity in Obese Mice","volume":"291","author":"Alexandre\u2010Santos B.","year":"2022","journal-title":"Life Sciences"},{"key":"e_1_2_10_61_1","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1097\/HJH.0b013e3283310e1b","article-title":"Long\u2010Term Treatment With an Angiotensin II Receptor Blocker Decreases Adipocyte Size and Improves Insulin Signaling in Obese Zucker Rats","volume":"27","author":"Mu\u00f1oz M. C.","year":"2009","journal-title":"Journal of Hypertension"},{"key":"e_1_2_10_62_1","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1097\/HJH.0000000000000506","article-title":"Blockade of the Renin\u2013Angiotensin System in Small Arteries and Anticontractile Function of Perivascular Adipose Tissue","volume":"33","author":"Rosei C. A.","year":"2015","journal-title":"Journal of Hypertension"},{"key":"e_1_2_10_63_1","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1161\/HYPERTENSIONAHA.113.01743","article-title":"Circulating Angiotensin II Gains Access to the Hypothalamus and Brain Stem During Hypertension via Breakdown of the Blood\u2013Brain Barrier","volume":"63","author":"Biancardi V. C.","year":"2014","journal-title":"Hypertension"},{"key":"e_1_2_10_64_1","doi-asserted-by":"crossref","DOI":"10.1155\/JBB\/2006\/27012","article-title":"The Adipose Renin\u2010Angiotensin System Modulates Systemic Markers of Insulin Sensitivity and Activates the Intrarenal Renin\u2010Angiotensin System","volume":"2006","author":"Kim S.","year":"2006","journal-title":"BioMed Research International"},{"key":"e_1_2_10_65_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41581-025-00950-5","article-title":"From Fat to Filter: The Effect of Adipose Tissue\u2010Derived Signals on Kidney Function","volume":"21","author":"Ahmed N.","year":"2025","journal-title":"Nature Reviews Nephrology"}],"container-title":["Endocrinology, Diabetes &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/edm2.70363","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/edm2.70363","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/edm2.70363","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T04:04:03Z","timestamp":1792469043000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/edm2.70363"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,19]]},"references-count":64,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1002\/edm2.70363"],"URL":"https:\/\/doi.org\/10.1002\/edm2.70363","archive":["Portico"],"relation":{},"ISSN":["2398-9238","2398-9238"],"issn-type":[{"value":"2398-9238","type":"print"},{"value":"2398-9238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,19]]},"assertion":[{"value":"2026-07-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70363"}}