{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:17:10Z","timestamp":1787318230593,"version":"build-2736575974"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2001,2]]},"abstract":"<jats:p>\n                    The  enzyme 11\u03b2-hydroxysteroid dehydrogenase (11\u03b2-HSD2) provides  mineralocorticoid receptor specificity for aldosterone by  metabolizing glucocorticoids to their receptor-inactive 11-dehydro  derivatives. The present study investigated the effects of the  aldosterone receptor antagonists spironolactone  and eplerenone on endothelial function in  liquorice-induced hypertension. Glycyrrhizic acid (GA), a recognized  inhibitor of 11\u03b2-HSD2, was supplemented to the drinking  water (3 g\/L) of Wistar-Kyoto rats over a period of 21 days. From days  8 to 21, spironolactone (5.8\u00b10.6 mg \u00b7  kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7  d\n                    <jats:sup>\u22121<\/jats:sup>\n                    ), eplerenone (182\u00b113 mg \u00b7  kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7  d\n                    <jats:sup>\u22121<\/jats:sup>\n                    ), or placebo was added to the chow  (n=7 animals per group). Endothelium-dependent or  -independent vascular function was assessed as the relaxation of  preconstricted aortic rings to acetylcholine or sodium nitroprusside,  respectively. In addition, aortic endothelial nitric  oxide synthase (eNOS) protein content, nitrate tissue levels, and  endothelin-1 (ET-1) protein levels were determined. GA increased  systolic blood pressure from 142\u00b18 to 185\u00b19 mm Hg  (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.01). In the GA group,  endothelium-dependent relaxation was impaired compared  with that in controls (73\u00b16% versus 99\u00b15%), whereas  endothelium-independent relaxation remained unchanged.  In the aortas of 11\u03b2-HSD2\u2013deficient rats, eNOS protein content and  nitrate tissue levels decreased (1114\u00b1128 versus 518\u00b177 \u03bcg\/g  protein,\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05). In contrast,  aortic ET-1 protein levels were enhanced by GA (308\u00b138 versus 497\u00b147  pg\/mg tissue,\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05). Both  spironolactone and eplerenone normalized blood pressure in animals on  GA (142\u00b19 and 143\u00b19 mm Hg, respectively, versus 189\u00b18  mm Hg in the placebo group;\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.01), restored  endothelium-dependent relaxation (96\u00b13% and 97\u00b13%,  respectively,\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.01 versus  placebo), blunted the decrease in vascular eNOS protein content and  nitrate tissue levels, and normalized vascular ET-1 levels. This is the  first study to demonstrate that aldosterone receptor  antagonism normalizes blood pressure, prevents upregulation of vascular  ET-1, restores NO-mediated endothelial dysfunction, and  thus, may advance as a novel and specific therapeutic approach in  11\u03b2-HSD2\u2013deficient hypertension.\n                  <\/jats:p>","DOI":"10.1161\/01.hyp.37.2.801","type":"journal-article","created":{"date-parts":[[2012,6,11]],"date-time":"2012-06-11T20:25:31Z","timestamp":1339446331000},"page":"801-805","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":66,"title":["Aldosterone Receptor Antagonism Normalizes Vascular Function in Liquorice-Induced Hypertension"],"prefix":"10.1161","volume":"37","author":[{"given":"Thomas","family":"Quaschning","sequence":"first","affiliation":[{"name":"From the Institute of Physiology (T.Q.), Cardiovascular Research,  University of Zu\u0308rich, Zu\u0308rich; the Cardiovascular Center (F.R.,  T.F.L.), Cardiology, University Hospital Zu\u0308rich, Zu\u0308rich; and the  Department of Clinical Research (S.S.), Inselspital, University of Bern, Bern,  Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Ruschitzka","sequence":"additional","affiliation":[{"name":"From the Institute of Physiology (T.Q.), Cardiovascular Research,  University of Zu\u0308rich, Zu\u0308rich; the Cardiovascular Center (F.R.,  T.F.L.), Cardiology, University Hospital Zu\u0308rich, Zu\u0308rich; and the  Department of Clinical Research (S.S.), Inselspital, University of Bern, Bern,  Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidney","family":"Shaw","sequence":"additional","affiliation":[{"name":"From the Institute of Physiology (T.Q.), Cardiovascular Research,  University of Zu\u0308rich, Zu\u0308rich; the Cardiovascular Center (F.R.,  T.F.L.), Cardiology, University Hospital Zu\u0308rich, Zu\u0308rich; and the  Department of Clinical Research (S.S.), Inselspital, University of Bern, Bern,  Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas F.","family":"Lu\u0308scher","sequence":"additional","affiliation":[{"name":"From the Institute of Physiology (T.Q.), Cardiovascular Research,  University of Zu\u0308rich, Zu\u0308rich; the Cardiovascular Center (F.R.,  T.F.L.), Cardiology, University Hospital Zu\u0308rich, Zu\u0308rich; and the  Department of Clinical Research (S.S.), Inselspital, University of Bern, Bern,  Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/355262a0"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113592"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0895-394"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.33.5.1179"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","unstructured":"Brem AS Bina RB King TC Morris DJ. 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