{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T04:40:25Z","timestamp":1768884025169,"version":"3.49.0"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Drug Investig"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1007\/s40261-025-01495-y","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T11:50:41Z","timestamp":1764676241000},"page":"49-55","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Pathophysiologic Mechanism for the Treatment of Salt-Sensitive Hypertension and Heart Failure: The Role of \u03b2-Arrestins"],"prefix":"10.1007","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9972-7151","authenticated-orcid":false,"given":"Steven G.","family":"Chrysant","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"key":"1495_CR1","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1001\/jama.2016.19043","volume":"317","author":"MH Farounzanfar","year":"2017","unstructured":"Farounzanfar MH, Liu R, Roth GA, Ng M, Biryukov S, et al. Global burden of hypertension and systolic blood pressure of at least 110 to 115 mmHg 1990\u20132015. JAMA. 2017;317:165\u201382.","journal-title":"JAMA"},{"key":"1495_CR2","doi-asserted-by":"publisher","first-page":"2993","DOI":"10.1002\/j.2040-4603.2012.tb00470.x","volume":"2","author":"JE Hall","year":"2012","unstructured":"Hall JE, Granger JP, do Carmo JM, da Silva AA, Dubinion J, George E, et al. Hypertension: physiology and pathophysiology. Compr Physiol. 2012;2:2993\u20132442.","journal-title":"Compr Physiol"},{"issue":"pt. 2","key":"1495_CR3","first-page":"II27","volume":"8","author":"MH Weinberger","year":"1986","unstructured":"Weinberger MH, Miller JZ, Luft FC, Grim CE, Fineberg NS. Definitions and characteristics of sensitivity and blood pressure resistance. Hypertension. 1986;8(pt. 2):II27\u201334.","journal-title":"Hypertension"},{"key":"1495_CR4","doi-asserted-by":"crossref","unstructured":"Poch E, Gonzalez D, Griner V, Bragulat E, Coca A, de la Sierra A. Molecular basis of salt sensitivity in human hypertension. Evaluation of renin-angiotensin-aldosterone system gene polymorphisms. Hypertension 2001; 38: 1204- 1209","DOI":"10.1161\/hy1101.099479"},{"key":"1495_CR5","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1007\/s11906-016-0677-y","volume":"18","author":"R Iatrino","year":"2016","unstructured":"Iatrino R, Manuanta P, Zagato L. Salt sensitivity: challenging and controversial phenotype in primary hypertension. Curr Hypertens Rep. 2016;18:70.","journal-title":"Curr Hypertens Rep"},{"key":"1495_CR6","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/0021-9681(80)90032-6","volume":"33","author":"CE Grim","year":"1980","unstructured":"Grim CE, Luft FC, Miller JZ. Racial differences in blood pressure in Evans county, Georgia: relationship to sodium intake and plasma renin activity. J Chronic Dis. 1980;33:87\u201394.","journal-title":"J Chronic Dis"},{"issue":"Suppl","key":"1495_CR7","doi-asserted-by":"publisher","first-page":"1S","DOI":"10.1093\/ajh\/5.4S.1S","volume":"5","author":"M Muntzer","year":"1992","unstructured":"Muntzer M, Drueke T. A comprehensive review of the salt and blood pressure relationship. Am J Hypertens. 1992;5(Suppl):1S-42S.","journal-title":"Am J Hypertens"},{"issue":"Suppl 1","key":"1495_CR8","first-page":"102","volume":"17","author":"FC Luft","year":"1991","unstructured":"Luft FC, Miller JZ, Grim CE, Fineberg NS, Christian JC, Daugherty SA, et al. Salt sensitivity and resistance of blood pressure: age and race factors in physiological responses. Hypertension. 1991;17(Suppl 1):102\u20138.","journal-title":"Hypertension"},{"key":"1495_CR9","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1097\/HJH.0b013e328316bb87","volume":"27","author":"J He","year":"2009","unstructured":"He J, Gu D, Chen J, Jaquish CE, Rao DC, Hixson JE, et al. Gender difference in blood pressure response to dietary sodium intervention in GenSalt study. J Hypertens. 2009;27:48\u201354.","journal-title":"J Hypertens"},{"key":"1495_CR10","doi-asserted-by":"publisher","first-page":"1970","DOI":"10.3390\/nu11091970","volume":"11","author":"A Grillo","year":"2019","unstructured":"Grillo A, Salvi L, Coruzzi P, Salvin P, Parati G. Sodium intake and hypertension. Nutrients. 2019;11:1970.","journal-title":"Nutrients"},{"key":"1495_CR11","doi-asserted-by":"publisher","first-page":"2489","DOI":"10.1001\/archinte.1997.00440420121013","volume":"157","author":"SG Chrysant","year":"1997","unstructured":"Chrysant SG, Weir MR, Weder AB, McCarron DA, Canossa Terris M, Cohen JD, et al. There are no racial, age, or weight differences in the effect of salt on blood pressure in salt-sensitive hypertensive patients. Arch Intern Med. 1997;157:2489\u201394.","journal-title":"Arch Intern Med"},{"key":"1495_CR12","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/0002-9343(80)90002-9","volume":"69","author":"T Fujita","year":"1980","unstructured":"Fujita T, Henry WL, Barter FC, Lake CF, Delea CS. Factors influencing blood pressure in salt sensitive patients with hypertension. Am J Med. 1980;69:334\u201344.","journal-title":"Am J Med"},{"key":"1495_CR13","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/0002-8703(83)90289-2","volume":"105","author":"RF Gillum","year":"1983","unstructured":"Gillum RF, Prineas RJ, Jeffrey RW. Non-pharmacologic therapy of hypertension: independent effects of weight reduction and sodium restriction in overweight borderline hypertensive patients. Am Heart J. 1983;105:129\u201333.","journal-title":"Am Heart J"},{"issue":"580","key":"1495_CR14","first-page":"585","volume":"321","author":"AP Rocchini","year":"1989","unstructured":"Rocchini AP, Key J, Bondie D, Chico R, Moorehead C, Katch V, et al. The effects of weight loss on the sensitivity of blood pressure to sodium in obese adolescents. N Engl J Med. 1989;321(580):585.","journal-title":"N Engl J Med"},{"key":"1495_CR15","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/ki.1982.32","volume":"21","author":"VM Campese","year":"1982","unstructured":"Campese VM, Romoff MS, Levitan D, Romoff MS, Goldstein DA, Massry SG. Abnormal relationship between sodium intake and sympathetic nervous system activity in salt-sensitive patients with essential hypertension. Kidney Int. 1982;21:371\u20138.","journal-title":"Kidney Int"},{"key":"1495_CR16","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1161\/01.HYP.6.6.820","volume":"6","author":"MI Koolen","year":"1984","unstructured":"Koolen MI, Van Bremmelen PV. Adrenergic activity and peripheral hemodynamics in relation to sodium sensitivity in patients with essential hypertension. Hypertension. 1984;6:820\u20135.","journal-title":"Hypertension"},{"key":"1495_CR17","first-page":"3","volume":"1","author":"E Ferrannini","year":"1989","unstructured":"Ferrannini E, De Fronzo RA. The asssociation of hypertension, diabetes, and obesity: a review. J Nephrol. 1989;1:3\u201315.","journal-title":"J Nephrol"},{"issue":"Suppl 1","key":"1495_CR18","first-page":"136","volume":"17","author":"ML Tuck","year":"1991","unstructured":"Tuck ML. Role of salt in the control of blood pressure in obesity and diabetes mellitus. Hypertension. 1991;17(Suppl 1):136\u201342.","journal-title":"Hypertension"},{"key":"1495_CR19","first-page":"287","volume":"10","author":"AP Rocchini","year":"2000","unstructured":"Rocchini AP. Obesity, hypertension, salt sensitivity and insulin resistance. Nutr Metab Cardiovasc Dis. 2000;10:287\u201394.","journal-title":"Nutr Metab Cardiovasc Dis"},{"key":"1495_CR20","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.793924","volume":"12","author":"LA Ertuglu","year":"2021","unstructured":"Ertuglu LA, Elijovich F, Laffer CL, Kirabo A. Salt-sensitivity of blood pressure and insulin resistance. Front Physiol. 2021;12:79392.","journal-title":"Front Physiol"},{"key":"1495_CR21","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1080\/14779072.2024.2364031","volume":"22","author":"SG Chrysant","year":"2024","unstructured":"Chrysant SG. The role of gut microbiota in the development of salt-sensitive hypertension and the possible preventive effects of exercise. Expert Rev Cardiovasc Ther. 2024;22:265\u201371.","journal-title":"Expert Rev Cardiovasc Ther"},{"key":"1495_CR22","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1097\/CRD.0000000000000518","volume":"32","author":"SG Chrysant","year":"2024","unstructured":"Chrysant SG. The interaction of kidneys and gut in the development of salt-sensitive hypertension. Cardiol Rev. 2024;32:356\u201361.","journal-title":"Cardiol Rev"},{"key":"1495_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2024.111410","volume":"124","author":"KD Singh","year":"2024","unstructured":"Singh KD, Karnik SS. Implications of \u03b2-arrestin biased signaling by angiotensin II type 1 receptor for cardiovascular drug discovery and therapeutics. Cell Signal. 2024;124:111410.","journal-title":"Cell Signal"},{"key":"1495_CR24","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1161\/HYPERTENSIONAHA.123.19419","volume":"81","author":"NM Mathieu","year":"2024","unstructured":"Mathieu NM, Nakagawa P, Grobe JL, Sigmund CD. Insights into the role of angiotensin-II AT1 receptor-dependent \u03b2-arrestin signaling in cardiovascular disease. Hypertension. 2024;81:6\u201316.","journal-title":"Hypertension"},{"key":"1495_CR25","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1161\/HYPERTENSIONAHA.117.09943","volume":"70","author":"P Zhabayeyev","year":"2017","unstructured":"Zhabayeyev P, Zhang H, Oudit GY. Is \u03b2-arrestin a magic bulett for heart failure treatment? Hypertension. 2017;70:887\u20139.","journal-title":"Hypertension"},{"key":"1495_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.cophys.2023.100723","volume":"37","author":"PC Nibley","year":"2024","unstructured":"Nibley PC, Shenoy SK. \u0392-adrenergic receptor signaling mediated by \u03b2-arrestins and its potential role in heart failure. Curr Opin Physiol. 2024;37:100723.","journal-title":"Curr Opin Physiol"},{"key":"1495_CR27","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1126\/science.2163110","volume":"248","author":"M Lohse","year":"1990","unstructured":"Lohse M, Renovik J, Codina J, et al. Beta-arrestin: a protein that regulates beta-adrenergic receptor function. Sciences. 1990;248:1547\u201350.","journal-title":"Sciences"},{"key":"1495_CR28","doi-asserted-by":"publisher","first-page":"17882","DOI":"10.1016\/S0021-9258(19)37125-X","volume":"267","author":"H Attramadal","year":"1992","unstructured":"Attramadal H, Arriza JL, Aoki C, et al. Beta-arrestin2, a novel member of the arrestin\/beta-arrestin gene family. J Biol Chem. 1992;267:17882\u201390.","journal-title":"J Biol Chem"},{"key":"1495_CR29","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1161\/HYPERTENSIONAHA.117.08550","volume":"70","author":"R Nakagawa","year":"2017","unstructured":"Nakagawa R, Sigmund CD. How is the brain renin\u2013angiotensin system regulated? Hypertension. 2017;70:10\u20138.","journal-title":"Hypertension"},{"key":"1495_CR30","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.cmet.2010.09.011","volume":"12","author":"JL Grobe","year":"2010","unstructured":"Grobe JL, Grobe CL, Beltz TG, Westphal SG, Morgan DA, Xu D, et al. The brain renin\u2013angiotensin system controls divergent efferent mechanisms to regulate fluid and energy balance. Cell Metab. 2010;12:431\u201342.","journal-title":"Cell Metab"},{"key":"1495_CR31","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1161\/01.RES.81.6.1021","volume":"81","author":"D Conner","year":"1997","unstructured":"Conner D, Mathier M, Mortensen R, et al. Beta-arrestin knockout mice appear normal but demonstrate altered cardiac responses to beta-adrenergic stimulation. Circ Res. 1997;81:1021\u20136.","journal-title":"Circ Res"},{"key":"1495_CR32","doi-asserted-by":"publisher","first-page":"2495","DOI":"10.1126\/science.286.5449.2495","volume":"286","author":"RA Bond","year":"1999","unstructured":"Bond RA, Lefkowitz RJ, Gainetdinov RR, et al. Enhanced morphine analgesia in mice lacking beta-arrestin2. Science. 1999;286:2495\u20138.","journal-title":"Science"},{"key":"1495_CR33","doi-asserted-by":"publisher","first-page":"124","DOI":"10.3389\/fphar.2019.00124","volume":"10","author":"RA Bond","year":"2019","unstructured":"Bond RA, Garcia-Rojas EYC, Hedge A, et al. Therapeutic potential of targeting \u03b2-arrestin. Front Pharmacol. 2019;10:124.","journal-title":"Front Pharmacol"},{"key":"1495_CR34","doi-asserted-by":"publisher","first-page":"R376","DOI":"10.1152\/ajpregu.00216.2014","volume":"307","author":"JP Coble","year":"2014","unstructured":"Coble JP, Cassell MD, Davis DR, Grobe JL, Sigmund CD. Activation of the renin-angiotensin system, specifically in the subfornical organ is sufficient to induce fluid intake. Am J Physiol Regul Integr Comp Physiol. 2014;307:R376\u201380.","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"1495_CR35","doi-asserted-by":"publisher","first-page":"R238","DOI":"10.1152\/ajpregu.00486.2014","volume":"308","author":"JP Coble","year":"2015","unstructured":"Coble JP, Grobe JL, Johnson AK, Sigmund CD. Mechanisms of brain renin angiotensin system-induced drinking and blood pressure: importance of the subfornical organ. Am J Physiol Regul Integr Comp Physiol. 2015;308:R238\u201349.","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"1495_CR36","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s11906-019-1011-2","volume":"22","author":"P Nakagawa","year":"2020","unstructured":"Nakagawa P, Gomez J, Grobe JL, Sigmund CD. The renin-angiotensin system in the central nervous system and its role in blood pressure regulation. Curr Hypertens Rep. 2020;22:7.","journal-title":"Curr Hypertens Rep"},{"key":"1495_CR37","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1080\/14740338.2023.2189236","volume":"22","author":"SG Chrysant","year":"2023","unstructured":"Chrysant SG. Superior stroke prevention with the angiotensin receptor blockers compared with other antihypertensive drugs. Expert Opin Drug Saf. 2023;22:125\u201331.","journal-title":"Expert Opin Drug Saf"},{"key":"1495_CR38","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1161\/01.HYP.0000033812.99089.92","volume":"40","author":"S Ito","year":"2002","unstructured":"Ito S, Komatsu K, Tsukamoto K, Kanmatsuse K, Sved AF. Ventrolateral medulla AT 1 receptors support blood pressure in hypertensive rats. Hypertension. 2002;40:552\u20139.","journal-title":"Hypertension"},{"key":"1495_CR39","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1161\/HYPERTENSIONAHA.111.00356","volume":"61","author":"AM Hilzendeger","year":"2013","unstructured":"Hilzendeger AM, Cassell MD, Davis DR, Stauss HM, Mark AL, Grobe JL, et al. Angiotensin type 1a receptors in the subcortical organ are required for deoxycorticosterone acetate-salt hypertension. Hypertension. 2013;61:716\u201322.","journal-title":"Hypertension"},{"key":"1495_CR40","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1152\/physrev.00038.2017","volume":"98","author":"SJ Forrester","year":"2018","unstructured":"Forrester SJ, Booz GW, Sigmund CD, Coffman TM, Kawai T, Rizzo V, et al. Angiotensin II signal transduction: an update on mechanisms on physiology and pathophysiology. Physiol Rev. 2018;98:1627\u2013738.","journal-title":"Physiol Rev"},{"key":"1495_CR41","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1161\/HYPERTENSIONAHA.120.15793","volume":"77","author":"M Zanaty","year":"2021","unstructured":"Zanaty M, Seara FAC, Nakagawa P, Deng G, Mathieu NM, Balarattabi K, et al. \u03b2-Arrestin-based agonist targeting the brain angiotensin II type 1 receptor increases aversion to saline and lowers blood pressure in DOCCA-salt hypertension. Hypertension. 2021;77:420\u201331.","journal-title":"Hypertension"},{"key":"1495_CR42","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.694135","volume":"12","author":"JC Sun","year":"2021","unstructured":"Sun JC, Ran X, Ge LJ, Xu MJ, Wang WZ. The release of nitric oxide is involved in the \u03b2-arrestin 1-induced antihypertensive effect in the rostral ventrolateral medulla. Front Physiol. 2021;12:694135.","journal-title":"Front Physiol"},{"key":"1495_CR43","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1042\/CS20180222","volume":"132","author":"A Carvalho-Calvao","year":"2018","unstructured":"Carvalho-Calvao A, Ogunlade B, Xu J, Silva-Alves CRAM, Mendes-Junior LG, et al. Central administration of TRV027 improves baroreflex sensitivity and vascular reactivity in spontaneously hypertensive rats. Clin Sci. 2018;132:1513\u201327.","journal-title":"Clin Sci"},{"key":"1495_CR44","doi-asserted-by":"publisher","first-page":"972","DOI":"10.1161\/HYPERTENSIONAHA.117.09817","volume":"70","author":"KA McCrink","year":"2017","unstructured":"McCrink KA, Maning J, Vu A, Jafferjee M, Marrero C, Brill A, et al. \u03b2-arrestin 2 improves post-myocardial infarction heart failure via sarco(endo)plasmic reticulum Ca+-ATPase-dependent positive inotropy in cardiomyocytes. Hypertension. 2017;70:972\u201381.","journal-title":"Hypertension"},{"key":"1495_CR45","doi-asserted-by":"publisher","first-page":"2364","DOI":"10.1093\/eurheartj\/ehx196","volume":"38","author":"PS Pang","year":"2017","unstructured":"Pang PS, Butler J, Collins SP, Cotter G, Davison BA, Ezekowitz JA, et al. Biased ligand of the angiotensin II type 1 receptor in patients with acute heart failure: a randomized, double-blind, placebo-controlled, phase IIB, dose ranging trial (BLAST-AHF). Eur Heart J. 2017;38:2364\u201373.","journal-title":"Eur Heart J"},{"key":"1495_CR46","first-page":"1057","volume":"5","author":"T Kashihara","year":"2020","unstructured":"Kashihara T, Kagagishi H, Nakada T, Numaga-Tomita T, Kadota S, Wolf EE, et al. \u03b2-Arrestin-biased AT 1 agonist of TRV027 causes a neonatal-specific sustained positive inotropic effect without increasing the heart rate. J Am Coll Cardiol Basic Transl Sci. 2020;5:1057\u201369.","journal-title":"J Am Coll Cardiol Basic Transl Sci"},{"key":"1495_CR47","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1161\/CIRCHEARTFAILURE.111.962571","volume":"4","author":"G Boerrigter","year":"2011","unstructured":"Boerrigter G, Lark MW, Whalen EJ, Soergel DG, Violin JD, Burnett JC. Cardiorenal actions of TRV120027, a novel \u03b2-arrestin-biased ligand at the angiotensin II type 1 receptor, in healthy and heart failure canines. A novel therapeutic strategy for acute heart failure. Heart Fail. 2011;4:770\u20138.","journal-title":"Heart Fail"},{"key":"1495_CR48","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1002\/jcph.111","volume":"53","author":"DG Soergel","year":"2013","unstructured":"Soergel DG, Subach RN, Cowan CL, Violin JD, Lark MW. Fist clinical experience with TRV027: pharmacokinetics and pharmacodynamics in healthy volunteers. J Clin Pharmacol. 2013;53:892\u20139.","journal-title":"J Clin Pharmacol"},{"key":"1495_CR49","doi-asserted-by":"publisher","first-page":"838","DOI":"10.3390\/pharmaceutics13060838","volume":"13","author":"A Rakib","year":"2021","unstructured":"Rakib A, Eva TA, Sami SA, Mitra S, Nafiz IH, Das A, et al. Beta arrestins in the treatment of heart failure related to hypertension: a comprehensive review. Pharmaceutics. 2021;13:838.","journal-title":"Pharmaceutics"},{"key":"1495_CR50","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1093\/cvr\/cvx147","volume":"113","author":"Y Wang","year":"2017","unstructured":"Wang Y, Jin L, Song Y, Zhang M, Shan D, Liu Y, et al. \u03b2-arrestin 2 mediates cardiac ischemia\u2013reperfusion injury via inhibiting GPCR-independent cell survival signaling. Cardiovasc Res. 2017;113:1615\u201326.","journal-title":"Cardiovasc Res"},{"key":"1495_CR51","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1160\/TH11-06-0430","volume":"107","author":"M Schaff","year":"2012","unstructured":"Schaff M, Receveur N, Boudron C, Ohlmann P, Lamza F, Gachet C, et al. \u0392-arrestin-1 participates in thrombosis and regulates integrin \u03b1 Ii\u03b2 3 signaling without affecting p2y receptors desensitization and function. Thromb Haemost. 2012;107:735\u201348.","journal-title":"Thromb Haemost"},{"key":"1495_CR52","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1172\/JCI36806","volume":"119","author":"RW Walters","year":"2009","unstructured":"Walters RW, Shukla AK, Kovacs JJ, Violin JD, DeWire SM, Lam CM, et al. \u0392-arrestin 1 mediates nicotinic acid-induced flushing but not its antilipolytic effect, in mice. J Clin Investig. 2009;119:1312\u201321.","journal-title":"J Clin Investig"},{"key":"1495_CR53","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0068351","volume":"8","author":"K Watari","year":"2013","unstructured":"Watari K, Nakaya M, Nishida M, Kim KM, Kurose H. \u03b2-Arrestin 2 in infiltrated macrophages inhibits excessive inflammation after myocardial infarction. PLoS ONE. 2013;8:e68351.","journal-title":"PLoS ONE"},{"key":"1495_CR54","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1038\/s41581-019-0244-2","volume":"16","author":"KT Mills","year":"2020","unstructured":"Mills KT, Stefanescou A, He J. The global epidemiology of hypertension. Nat Rev Nephrol. 2020;16:223\u201337.","journal-title":"Nat Rev Nephrol"},{"key":"1495_CR55","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1186\/s12882-023-03391-z","volume":"24","author":"Y Liu","year":"2023","unstructured":"Liu Y, He Q, Lin Q, Tian M, Li X, Yao X, et al. Global incidence and death estimates of chronic kidney disease due to hypertension from 1990 to 2019, an etiological analysis of the global burden of diseases 2019 study. BMC Nephrol. 2023;24:352.","journal-title":"BMC Nephrol"},{"key":"1495_CR56","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1097\/HJH.0000000000002021","volume":"37","author":"BM Egan","year":"2018","unstructured":"Egan BM, Kjeldsen SE, Grassi G, Esler M, Mancia G. The global burden of hypertension exceeds 1.4 billion people: should systolic blood pressure target below 130 become the universal standard? J Hypertens. 2018;37:1148\u201353.","journal-title":"J Hypertens"},{"key":"1495_CR57","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1007\/s40256-024-00641-9","volume":"24","author":"H Hiraiwa","year":"2024","unstructured":"Hiraiwa H, Okumura T, Murohara T. Drug therapy for acute and chronic heart failure with preserved ejection fraction with hypertension: a state-of-the-art review. Am J Cardiovasc Drugs. 2024;24:343\u201369.","journal-title":"Am J Cardiovasc Drugs"},{"key":"1495_CR58","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1016\/j.jacc.2023.12.024","volume":"83","author":"TM Maddox","year":"2024","unstructured":"Maddox TM, Januzzi JL, Allen LA, Breathertt K, Brouse S, Butler J, et al. 2024 ACC expert consensus decision pathway for treatment of heart failure with reduced ejection fraction: a report of the American College of Cardiology solution set oversight committee. J Am Coll Cardiol. 2024;83:1444\u201388.","journal-title":"J Am Coll Cardiol"},{"key":"1495_CR59","doi-asserted-by":"publisher","first-page":"9841","DOI":"10.1021\/acs.jmedchem.8b00435","volume":"61","author":"L Tan","year":"2018","unstructured":"Tan L, Yan W, McCorvy JD, Cheng J. Biased ligands of G protein-coupled receptors (GOCRs): structure-functional selectivity relationships (SFSRs) and therapeutic potential. J Med Chem. 2018;61:9841\u201378.","journal-title":"J Med Chem"},{"key":"1495_CR60","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1124\/jpet.110.173005","volume":"335","author":"JD Violin","year":"2010","unstructured":"Violin JD, DeWire SM, Yamashita D, Rominger DH, Nguyen L, Schiller K, et al. Selectively engaging \u03b2-arrestins at the angiotensin II type 1 receptor reduces blood pressure and increases cardiac performance. J Pharmacol Exp Ther. 2010;335:572\u20139.","journal-title":"J Pharmacol Exp Ther"},{"key":"1495_CR61","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1016\/S0140-6736(21)01330-1","volume":"398","author":"M Ezzati","year":"2021","unstructured":"Ezzati M. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet. 2021;398:957\u2013980a.","journal-title":"Lancet"},{"key":"1495_CR62","first-page":"1057","volume":"5","author":"T Kashihara","year":"2020","unstructured":"Kashihara T, Kagagishi H, Nakada T, Numaga-Tomita T, Kadota S, Wolf EE, et al. \u03b2-Arrestin-biased AT1 agonist of TRV027 causes a neonatal-specific sustained positive inotropic effect without increasing the heart rate. J Am Coll Cardiol Basic Transl Sci. 2020;5:1057\u201369.","journal-title":"J Am Coll Cardiol Basic Transl Sci"},{"key":"1495_CR63","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.01336","volume":"9","author":"S Mangmool","year":"2018","unstructured":"Mangmool S, Parichatikanond W, Kurose H. Therapeutic targets for treatment of heart failure: focus on GRKs and \u03b2-arrestins affecting \u03b2AR signaling. Front Pharmacol. 2018;9:2018.","journal-title":"Front Pharmacol"},{"key":"1495_CR64","doi-asserted-by":"publisher","first-page":"47","DOI":"10.4330\/wjc.v11.i2.47","volume":"11","author":"A Lymperopoulos","year":"2019","unstructured":"Lymperopoulos A, Wetz SL, Pollard CM, Desimine VL, Maning J, McCrink K. Not all arrestins are created equal: therapeutic implications of the functional diversity of the \u03b2-arrestins in the heart. World J Cardiol. 2019;11:47\u201356.","journal-title":"World J Cardiol"}],"container-title":["Clinical Drug Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40261-025-01495-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40261-025-01495-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40261-025-01495-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T16:03:12Z","timestamp":1768838592000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40261-025-01495-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,2]]},"references-count":64,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["1495"],"URL":"https:\/\/doi.org\/10.1007\/s40261-025-01495-y","relation":{},"ISSN":["1173-2563","1179-1918"],"issn-type":[{"value":"1173-2563","type":"print"},{"value":"1179-1918","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,2]]},"assertion":[{"value":"18 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The author has no competing interests to declare that are relevant to the content of this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of Interest"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"No datasets were generated or analyzed during the current study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of data and material"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"This manuscript was independently conceived and written by SGC. SGC is the sole author of this article and is fully responsible for its integrity.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author\u2019s contributions"}}]}}