{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T19:32:38Z","timestamp":1791660758623,"version":"4.3.4"},"reference-count":33,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,4,1]]},"abstract":"<jats:p>Recently, aldosterone has been shown to activate local renin-angiotensin system in vitro. To elucidate the potential role of local renin-angiotensin system in aldosterone-induced cardiovascular injury, we investigated the effects of selective mineralocorticoid receptor (MR) antagonist eplerenone (EPL), angiotensin (Ang) II type 1 receptor antagonist candesartan (ARB), and superoxide dismutase mimetic tempol (TEM) on the development of hypertension, vascular injury, oxidative stress, and inflammatory-related gene expression in aldosterone-treated hypertensive rats. The increased systolic blood pressure and vascular inflammatory changes were attenuated by cotreatment either with EPL, ARB, or TEM. Aldosterone increased angiotensin-converting enzyme expression in the aortic tissue; its effects were blocked by EPL but not by ARB or TEM. Aldosterone also increased Ang II contents in the aortic tissue in the presence of low circulating Ang II concentrations. Aldosterone induced expression of various inflammatory-related genes, whose effects were abolished by EPL, whereas the inhibitory effects of ARB and TEM varied depending on the gene. Aldosterone caused greater accumulation of the oxidant stress marker 4-hydroxy-2-neonenal in the endothelium; its effect was abolished by EPL, ARB, or TEM. Aldosterone increased mRNA levels of reduced nicotinamide adenine dinucleotide phosphate oxidase components; their effect was abolished by EPL, whereas ARB and TEM decreased only the p47phox mRNA level but not that of p22phox or gp91phox. The present findings suggest that the Ang II-dependent pathway resulting from vascular angiotensin-converting enzyme up-regulation and Ang II-independent pathway are both involved in the underlying mechanisms resulting in the development of hypertension, vascular inflammation, and oxidative stress induced by aldosterone.<\/jats:p>","DOI":"10.1210\/en.2006-1157","type":"journal-article","created":{"date-parts":[[2007,1,12]],"date-time":"2007-01-12T01:34:41Z","timestamp":1168565681000},"page":"1688-1696","source":"Crossref","is-referenced-by-count":91,"title":["Angiotensin II Receptor Type 1-Mediated Vascular Oxidative Stress and Proinflammatory Gene Expression in Aldosterone-Induced Hypertension: The Possible Role of Local Renin-Angiotensin System"],"prefix":"10.1210","volume":"148","author":[{"given":"Yuki","family":"Hirono","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanobu","family":"Yoshimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Sugiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Sakurada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Takai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naohiko","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayoshi","family":"Shichiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Hirata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613552283900_R1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.mce.2003.10.054","article-title":"Aldosterone, mineralocorticoid receptors and vascular inflammation.","volume":"217","author":"Funder","year":"2004","journal-title":"Mol Cell Endocrinol"},{"key":"2020071613552283900_R2","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.amjcard.2006.03.009","article-title":"Role of aldosterone blockade for treatment of heart failure and post-acute myocardial infarction.","volume":"97","author":"Greenberg","year":"2006","journal-title":"Am J Cardiol"},{"key":"2020071613552283900_R3","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1161\/01.HYP.33.4.981","article-title":"Angiotensin AT1 receptor subtype as a cardiac target of aldosterone: role in aldosterone-salt-induced fibrosis.","volume":"33","author":"Robert","year":"1999","journal-title":"Hypertension"},{"key":"2020071613552283900_R4","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.1161\/01.CIR.0000131860.80444.AB","article-title":"Aldosterone potentiates angiotensin II-induced signaling in vascular smooth muscle cells.","volume":"109","author":"Mazak","year":"2004","journal-title":"Circulation"},{"key":"2020071613552283900_R5","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1161\/01.RES.0000180753.63183.95","article-title":"Aldosterone and angiotensin II synergistically induce mitogenic response in vascular smooth muscle cells.","volume":"97","author":"Min","year":"2005","journal-title":"Circ Res"},{"key":"2020071613552283900_R6","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1161\/01.HYP.0000140771.21243.ed","article-title":"Mechanism for aldosterone potentiation of angiotensin II-stimulated rat arterial smooth muscle cell proliferation.","volume":"44","author":"Xiao","year":"2004","journal-title":"Hypertension"},{"key":"2020071613552283900_R7","doi-asserted-by":"crossref","first-page":"3900","DOI":"10.1210\/en.2004-1674","article-title":"Aldosterone induces angiotensin converting enzyme gene expression via a JAK2-dependent pathway in rat endothelial cells.","volume":"146","author":"Sugiyama","year":"2005","journal-title":"Endocrinology"},{"key":"2020071613552283900_R8","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1161\/01.HYP.37.2.781","article-title":"Long-term antioxidant administration attenuates mineralocorticoid hypertension and renal inflammatory response.","volume":"37","author":"Beswick","year":"2001","journal-title":"Hypertension"},{"key":"2020071613552283900_R9","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0895-7061(04)00811-8","article-title":"Involvement of oxidative stress in the profibrotic action of aldosterone. Interaction with the renin-angiotensin system.","volume":"17","author":"Iglarz","year":"2004","journal-title":"Am J Hypertens"},{"key":"2020071613552283900_R10","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1016\/S0002-9440(10)64454-9","article-title":"Aldosterone-induced inflammation in the rat heart: role of oxidative stress.","volume":"161","author":"Sun","year":"2002","journal-title":"Am J Pathol"},{"key":"2020071613552283900_R11","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1089\/ars.2005.7.1302","article-title":"Reactive oxygen species as mediators of calcium signaling by angiotensin II: implications in vascular physiology and pathophysiology.","volume":"7","author":"Touyz","year":"2005","journal-title":"Antioxid Redox Signal"},{"key":"2020071613552283900_R12","doi-asserted-by":"crossref","first-page":"3331","DOI":"10.1210\/en.2003-1583","article-title":"Antioxidant effect of adrenomedullin on angiotensin II-induced reactive oxygen species generation in vascular smooth muscle cells.","volume":"145","author":"Yoshimoto","year":"2004","journal-title":"Endocrinology"},{"key":"2020071613552283900_R13","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1291\/hypres.28.165","article-title":"Adrenomedullin inhibits angiotensin II-induced oxidative stress and gene expression in rat endothelial cells.","volume":"28","author":"Yoshimoto","year":"2005","journal-title":"Hypertens Res"},{"key":"2020071613552283900_R14","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/sj.bjp.0702833","article-title":"Anti-atherosclerotic effects of an angiotensin converting enzyme inhibitor and an angiotensin II antagonist in Cynomolgus monkeys fed a high-cholesterol diet.","volume":"128","author":"Miyazaki","year":"1999","journal-title":"Br J Pharmacol"},{"key":"2020071613552283900_R15","first-page":"F902","article-title":"Dietary Na and ACE inhibition effects on renal tissue angiotensin I and II and ACE activity in rats","volume":"262","author":"Fox","year":"1992","journal-title":"Am J Physiol"},{"key":"2020071613552283900_R16","first-page":"145","article-title":"Induction and nuclear translocation of thioredoxin by oxidative damage in the mouse kidney: independence of tubular necrosis and sulfhydryl depletion.","volume":"77","author":"Tanaka","year":"1997","journal-title":"Lab Invest"},{"key":"2020071613552283900_R17","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1161\/01.HYP.0000118519.66430.22","article-title":"Possible contributions of reactive oxygen species and mitogen-activated protein kinase to renal injury in aldosterone\/salt-induced hypertensive rats.","volume":"43","author":"Nishiyama","year":"2004","journal-title":"Hypertension"},{"key":"2020071613552283900_R18","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/S0165-6147(03)00233-5","article-title":"The vascular NAD(P)H oxidases as therapeutic targets in cardiovascular diseases.","volume":"24","author":"Cai","year":"2003","journal-title":"Trends Pharmacol Sci"},{"key":"2020071613552283900_R19","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1161\/01.CIR.104.2.137","article-title":"Aldosterone induces angiotensin-converting-enzyme gene expression in cultured neonatal rat cardiocytes.","volume":"104","author":"Harada","year":"2001","journal-title":"Circulation"},{"key":"2020071613552283900_R20","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1291\/hypres.28.925","article-title":"Cardioprotective mechanisms of spironolactone associated with the angiotensin-converting enzyme\/epidermal growth factor receptor\/extracellular signal-regulated kinases, NAD(P)H oxidase\/lectin-like oxidized low-density lipoprotein receptor-1, and Rho-kinase pathways in aldosterone\/salt-induced hypertensive rats.","volume":"28","author":"Nakano","year":"2005","journal-title":"Hypertens Res"},{"issue":"Suppl 1","key":"2020071613552283900_R21","first-page":"1","article-title":"Local expression and pathophysiological role of renin-angiotensin in the blood vessels and heart","volume":"88","author":"Dzau","year":"1993","journal-title":"Basic Res Cardiol"},{"key":"2020071613552283900_R22","first-page":"S13","article-title":"Role of vascular angiotensin converting enzyme in hypertension","volume":"6","author":"Miyazaki","year":"1988","journal-title":"J Hypertens Suppl"},{"key":"2020071613552283900_R23","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1172\/JCI21398","article-title":"Inhibition of diabetic nephropathy by a decoy peptide corresponding to the \u201chandle\u201d region for nonproteolytic activation of prorenin.","volume":"114","author":"Ichihara","year":"2004","journal-title":"J Clin Invest"},{"key":"2020071613552283900_R24","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1172\/JCI0214276","article-title":"Pivotal role of the renin\/prorenin receptor in angiotensin II production and cellular responses to renin.","volume":"109","author":"Nguyen","year":"2002","journal-title":"J Clin Invest"},{"key":"2020071613552283900_R25","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/S0891-5849(02)00789-X","article-title":"The vascular NADPH oxidase subunit p47phox is involved in redox-mediated gene expression.","volume":"32","author":"Brandes","year":"2002","journal-title":"Free Radic Biol Med"},{"key":"2020071613552283900_R26","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1161\/01.HYP.0000154365.30593.d3","article-title":"Aldosterone activates vascular p38MAP kinase and NADPH oxidase via c-Src.","volume":"45","author":"Callera","year":"2005","journal-title":"Hypertension"},{"key":"2020071613552283900_R27","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1161\/01.HYP.0000226054.53527.bb","article-title":"Molecular mechanism of the inhibitory effect of aldosterone on endothelial NO synthase activity.","volume":"48","author":"Nagata","year":"2006","journal-title":"Hypertension"},{"key":"2020071613552283900_R28","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1097\/00041552-200103000-00011","article-title":"Non-genomic actions of aldosterone: role in hypertension.","volume":"10","author":"Funder","year":"2001","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"2020071613552283900_R29","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1161\/01.HYP.0000201443.63240.a7","article-title":"Effects of aldosterone on the vasculature.","volume":"47","author":"Schiffrin","year":"2006","journal-title":"Hypertension"},{"key":"2020071613552283900_R30","doi-asserted-by":"crossref","first-page":"623","DOI":"10.3109\/10715769809065818","article-title":"Lipid peroxidation and biogenic aldehydes: from the identification of 4-hydroxynonenal to further achievements in biopathology.","volume":"28","author":"Comporti","year":"1998","journal-title":"Free Radic Res"},{"key":"2020071613552283900_R31","doi-asserted-by":"crossref","first-page":"R277","DOI":"10.1152\/ajpregu.00758.2002","article-title":"Vascular NAD(P)H oxidases: specific features, expression, and regulation","volume":"285","author":"Lassegue","year":"2003","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"2020071613552283900_R32","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1161\/01.CIR.104.1.79","article-title":"Genetic demonstration of p47phox-dependent superoxide anion production in murine vascular smooth muscle cells.","volume":"104","author":"Lavigne","year":"2001","journal-title":"Circulation"},{"key":"2020071613552283900_R33","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1161\/hh0202.103615","article-title":"Essential role of the NADPH oxidase subunit p47(phox) in endothelial cell superoxide production in response to phorbol ester and tumor necrosis factor-\u03b1.","volume":"90","author":"Li","year":"2002","journal-title":"Circ Res"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/148\/4\/1688\/9035279\/endo1688.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/148\/4\/1688\/9035279\/endo1688.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T00:57:51Z","timestamp":1594947471000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/148\/4\/1688\/2501763"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,4,1]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2007,4,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2006-1157","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,4,1]]}}}