{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:46:12Z","timestamp":1791121572789,"version":"4.1.0"},"reference-count":20,"publisher":"The Endocrine Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,3,1]]},"abstract":"<jats:p>In epithelial tissues such as kidney, mineralocorticoid receptors (MR) are protected against glucocorticoid occupancy by the enzyme 11\u03b2-hydroxysteroid dehydrogenase (11\u03b2HSD) type 2. If the enzyme is congenitally inactive, or blocked by carbenoxolone, physiologic glucocorticoids act as MR agonists in such tissues. In most nonepithelial tissues, including cardiomyocytes, 11\u03b2HSD2 is expressed at minimal levels; in these tissues physiologic glucocorticoids act as MR antagonists, with the basis for this tissue selectivity currently unknown. Vascular smooth muscle cells (VSMC) express MR and 11\u03b2HSD1\/2, with 11\u03b2HSD1 reported to show uncharacteristic oxidase activity, so that VSMC thus constitute a potential physiologic aldosterone target tissue. Because mineralocorticoid\/salt administration triggers marked inflammatory responses in coronary vasculature, we reasoned that VSMC (like epithelial) MR may be activated by glucocorticoids if the protective enzyme is blocked. We thus gave uninephrectomized rats 0.9% NaCl solution to drink, and deoxycorticosterone (DOC, as a single 20 mg sc dose) or carbenoxolone (CBX, 2.5 mg\/d in the drinking solution). Both DOC and CBX increased systolic blood pressure, heart, and kidney weight, and expression of cyclooxygenase 2, ED-1-positive macrophages, and osteopontin, with effects of both DOC and CBX blocked by the selective MR antagonist eplerenone. These findings suggest that local glucocorticoid excess, reflecting lower VSMC 11\u03b2HSD1\/2 activity may mimic systemic mineralocorticoid excess, and play a direct etiologic role in coronary vascular inflammatory responses under circumstances of a high salt intake.<\/jats:p>","DOI":"10.1210\/en.2002-220926","type":"journal-article","created":{"date-parts":[[2003,2,13]],"date-time":"2003-02-13T17:05:31Z","timestamp":1045155931000},"page":"1121-1125","source":"Crossref","is-referenced-by-count":100,"title":["Early Inflammatory Responses in Experimental Cardiac Hypertrophy and Fibrosis: Effects of 11\u03b2-Hydroxysteroid Dehydrogenase Inactivation"],"prefix":"10.1210","volume":"144","author":[{"given":"Morag J.","family":"Young","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Moussa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rod","family":"Dilley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Funder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613533253100_R1","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":"2020071613533253100_R2","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":"2020071613533253100_R3","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":"2020071613533253100_R4","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1093\/ajh\/4.1.51","article-title":"Coronary vascular remodeling and myocardial fibrosis in the rat with renovascular hypertension. Response to captopril.","volume":"4","author":"Jalil","year":"1991","journal-title":"Am J Hypertens"},{"key":"2020071613533253100_R5","first-page":"E657","article-title":"Determinants of cardiac fibrosis in experimental hypermineralocorticoid states","volume":"269","author":"Young","year":"1995","journal-title":"Am J Physiol"},{"key":"2020071613533253100_R6","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1093\/cvr\/26.7.671","article-title":"Reactive and reparative myocardial fibrosis in arterial hypertension in the rat.","volume":"26","author":"Brilla","year":"1992","journal-title":"Cardiovasc Res"},{"key":"2020071613533253100_R7","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":"2020071613533253100_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":"2020071613533253100_R9","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":"2020071613533253100_R10","doi-asserted-by":"crossref","first-page":"3871","DOI":"10.1210\/endo.141.10.7711","article-title":"Aldosterone: a mediator of myocardial necrosis and renal arteriopathy.","volume":"141","author":"Rocha","year":"2000","journal-title":"Endocrinology"},{"key":"2020071613533253100_R11","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1161\/hyp.39.2.614","article-title":"Cardiac damage prevention by eplerenone: comparison with low sodium diet or potassium loading.","volume":"39","author":"Martinez","year":"2002","journal-title":"Hypertension"},{"key":"2020071613533253100_R12","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1161\/01.HYP.35.5.1099","article-title":"Role of 11\u03b2-hydroxysteroid dehydrogenase in nongenomic aldosterone effects in human arteries.","volume":"35","author":"Alzamora","year":"2000","journal-title":"Hypertension"},{"key":"2020071613533253100_R13","first-page":"F672","article-title":"Glucocorticoid receptors mediate mineralocorticoid-like effects in cultured collecting duct cells","volume":"259","author":"Naray-Fejes-Toth","year":"1990","journal-title":"Am J Physiol"},{"key":"2020071613533253100_R14","doi-asserted-by":"crossref","first-page":"3234","DOI":"10.1096\/fasebj.4.14.2172062","article-title":"Apparent mineralocorticoid excess, pseudohypoaldosteronism, and urinary electrolyte excretion: toward a redefinition of mineralocorticoid action.","volume":"4","author":"Funder","year":"1990","journal-title":"FASEB J"},{"key":"2020071613533253100_R15","doi-asserted-by":"crossref","first-page":"4145","DOI":"10.1210\/endo.137.10.8828470","article-title":"High glucose stimulates aldosterone-induced hypertrophy via type I mineralocorticoid receptors in neonatal rat cardiomyocytes.","volume":"137","author":"Sato","year":"1996","journal-title":"Endocrinology"},{"key":"2020071613533253100_R16","first-page":"E649","article-title":"ICV infusion of corticosterone antagonizes ICV-aldosterone hypertension","volume":"258","author":"Gomez-Sanchez","year":"1990","journal-title":"Am J Physiol"},{"key":"2020071613533253100_R17","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.1172\/JCI119031","article-title":"Osteopontin is produced by rat cardiac fibroblasts and mediates A(II)-induced DNA synthesis and collagen gel contraction.","volume":"98","author":"Ashizawa","year":"1996","journal-title":"J Clin Invest"},{"key":"2020071613533253100_R18","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1161\/01.HYP.33.2.663","article-title":"Myocardial osteopontin expression coincides with the development of heart failure.","volume":"33","author":"Singh","year":"1999","journal-title":"Hypertension"},{"key":"2020071613533253100_R19","doi-asserted-by":"crossref","first-page":"H1802","DOI":"10.1152\/ajpheart.01096.2001","article-title":"Aldosterone induces a vascular inflammatory phenotype in the rat heart","volume":"283","author":"Rocha","year":"2002","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2020071613533253100_R20","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1161\/01.HYP.33.1.232","article-title":"Role of aldosterone in renal vascular injury in stroke-prone hypertensive rats.","volume":"33","author":"Rocha","year":"1999","journal-title":"Hypertension"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/144\/3\/1121\/9020342\/endo1121.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/144\/3\/1121\/9020342\/endo1121.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T20:53:35Z","timestamp":1594932815000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/144\/3\/1121\/2502355"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,3,1]]},"references-count":20,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2003,3,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2002-220926","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,3,1]]}}}