{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T12:59:10Z","timestamp":1791118750874,"version":"4.1.0"},"reference-count":33,"publisher":"The Endocrine Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Aldosterone has been thought to act primarily on epithelia to regulate fluid and electrolyte homeostasis. Mineralocorticoid receptors (MR), however, are also expressed in nonepithelial tissues, such as the heart and vascular smooth muscle. Recently, pathophysiological effects of nonepithelial MR activation by aldosterone have been demonstrated in the context of inappropriate mineralocorticoid levels for salt status, including coronary vascular inflammation and cardiac fibrosis. These effects are mostly prevented by the concomitant administration of MR antagonists, but to date, no equivalent studies have determined whether MR blockade can reverse established inflammation and fibrosis. Uninephrectomized rats maintained on 0.9% NaCl solution to drink were treated as follows: group 1 served as controls; group 2 received deoxycorticosterone (DOC; 20 mg\/wk) for 4 wk until death, and group 3 received DOC for 8 wk. Group 4 received DOC for 4 wk and no steroid from wk 5\u20138; group 5 received DOC for 8 wk and eplerenone in their chow during wk 5\u20138. DOC progressively raised cardiac collagen accumulation at 4 and 8 wk. Rats given DOC for 4 wk and killed at 8 wk showed levels of fibrosis identical to those in animals killed at 4 wk, i.e. persistently elevated above control values. Rats given DOC for 8 wk and eplerenone for the second half of the period showed cardiac collagen levels indistinguishable from control values. Values for inflammatory marker and NAD(P)H oxidase subunit expression in coronary vessels showed a similar pattern of response, with minor variation. Thus, MR antagonists do not only prevent cardiac fibrosis, but also reverse cardiac fibrosis once it is established. In addition, the continuing vascular inflammatory response and fibrosis after DOC withdrawal (group 4) support a role for activation of vascular MR by endogenous glucocorticoids in the context of tissue damage and generation of reactive oxygen species.<\/jats:p>","DOI":"10.1210\/en.2004-0005","type":"journal-article","created":{"date-parts":[[2004,4,6]],"date-time":"2004-04-06T00:35:11Z","timestamp":1081211711000},"page":"3153-3157","source":"Crossref","is-referenced-by-count":88,"title":["Eplerenone, But Not Steroid Withdrawal, Reverses Cardiac Fibrosis in Deoxycorticosterone\/ Salt-Treated Rats"],"prefix":"10.1210","volume":"145","author":[{"given":"Morag","family":"Young","sequence":"first","affiliation":[{"name":"Prince Henry\u2019s Institute for Medical Research, Clayton, 3168 Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Funder","sequence":"first","affiliation":[{"name":"Prince Henry\u2019s Institute for Medical Research, Clayton, 3168 Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613164185300_R1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1161\/01.HYP.26.6.971","article-title":"Biological determinants of aldosterone-induced cardiac fibrosis in rats.","volume":"26","author":"Robert","year":"1995","journal-title":"Hypertension"},{"key":"2020071613164185300_R2","first-page":"893","article-title":"Mineralocorticoid excess, dietary sodium, and myocardial fibrosis.","volume":"120","author":"Brilla","year":"1992","journal-title":"J Lab Clin Med"},{"key":"2020071613164185300_R3","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1172\/JCI117269","article-title":"Mineralocorticoids, hypertension, and cardiac fibrosis.","volume":"93","author":"Young","year":"1994","journal-title":"J Clin Invest"},{"key":"2020071613164185300_R4","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1006\/jmcc.1993.1066","article-title":"Anti-aldosterone treatment and the prevention of myocardial fibrosis in primary and secondary hyperaldosteronism.","volume":"25","author":"Brilla","year":"1993","journal-title":"J Mol Cell Cardiol"},{"key":"2020071613164185300_R5","first-page":"E883","article-title":"The renin-angiotensin-aldosterone system in experimental mineralocorticoid-salt-induced cardiac fibrosis","volume":"271","author":"Young","year":"1996","journal-title":"Am J Physiol"},{"key":"2020071613164185300_R6","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0039-128X(96)00020-7","article-title":"Mineralocorticoids, salt, hypertension: effects on the heart.","volume":"61","author":"Young","year":"1996","journal-title":"Steroids"},{"key":"2020071613164185300_R7","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1161\/01.HYP.24.1.30","article-title":"Increased cardiac types I and III collagen mRNAs in aldosterone-salt hypertension.","volume":"24","author":"Robert","year":"1994","journal-title":"Hypertension"},{"key":"2020071613164185300_R8","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/S0022-2828(95)90359-3","article-title":"Temporal differences in fibroblast proliferation and phenotype expression in response to chronic administration of angiotensin II or aldosterone.","volume":"27","author":"Campbell","year":"1995","journal-title":"J Mol Cell Cardiol"},{"key":"2020071613164185300_R9","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1210\/en.2002-220926","article-title":"Early inflammatory responses in experimental cardiac hypertrophy and fibrosis: effects of 11\u03b2-hydroxysteroid dehydrogenase inactivation.","volume":"144","author":"Young","year":"2003","journal-title":"Endocrinology"},{"key":"2020071613164185300_R10","doi-asserted-by":"crossref","first-page":"3625","DOI":"10.1210\/endo.142.8.8339","article-title":"Experimental cardiac fibrosis: differential time course of responses to mineralocorticoid-salt administration.","volume":"142","author":"Fujisawa","year":"2001","journal-title":"Endocrinology"},{"key":"2020071613164185300_R11","first-page":"H1802","article-title":"Aldosterone induces a vascular inflammatory phenotype in the rat heart","volume":"283","author":"Rocha","year":"2002","journal-title":"Am J Physiol"},{"key":"2020071613164185300_R12","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1161\/01.HYP.31.1.451","article-title":"Mineralocorticoid blockade reduces vascular injury in stroke-prone hypertensive rats.","volume":"31","author":"Rocha","year":"1998","journal-title":"Hypertension"},{"key":"2020071613164185300_R13","doi-asserted-by":"crossref","first-page":"2700","DOI":"10.1161\/01.CIR.102.22.2700","article-title":"Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized aldactone evaluation study (RALES). 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