{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:43:10Z","timestamp":1787319790539,"version":"build-2736575974"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"25","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2001,6,26]]},"abstract":"<jats:p>\n                    <jats:italic>Background<\/jats:italic>\n                    \u2014The enzyme 11\u03b2-hydroxysteroid dehydrogenase (11\u03b2-HSD) prevents inappropriate activation of the nonselective mineralocorticoid receptors by glucocorticoids. Renal activity of 11\u03b2-HSD is decreased in patients with apparent mineralocorticoid excess (SAME), licorice-induced hypertension, and essential hypertension. Although expressed in vascular cells, the role of 11\u03b2-HSD in the regulation of vascular tone remains to be determined.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Methods and Results<\/jats:italic>\n                    \u2014Glycyrrhizic acid (GA; 50 mg\/kg IP, twice daily for 7 days) caused a significant inhibition of 11\u03b2-HSD activity and induced hypertension in Wistar-Kyoto rats (157 versus 127 mm Hg in controls;\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.01). After 11\u03b2-HSD inhibition, aortic endothelial nitric oxide (NO) synthase (eNOS) protein content, nitrate tissue levels, and acetylcholine-induced release of NO were blunted (all\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05 versus controls). In contrast, vascular prepro-endothelin (ET)-1 gene expression, ET-1 protein levels, and vascular reactivity to ET-1 were enhanced by GA treatment (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05 versus controls). Chronic ET\n                    <jats:sub>A<\/jats:sub>\n                    receptor blockade with LU135252 (50 mg \u00b7 kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7 d\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) normalized blood pressure, ET-1 tissue content, vascular reactivity to ET-1, vascular eNOS protein content, and nitrate tissue levels and improved NO-mediated endothelial function in GA-treated rats (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05 to 0.01 versus untreated and verapamil-treated controls). In human endothelial cells, GA increased production of ET-1 in the presence of corticosterone, which indicates that activation of the vascular ET-1 system by 11\u03b2-HSD inhibition can occur independently of changes in blood pressure but is dependent on the presence of glucocorticoids.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Conclusions<\/jats:italic>\n                    \u2014Chronic ET\n                    <jats:sub>A<\/jats:sub>\n                    receptor blockade normalizes blood pressure, prevents upregulation of vascular ET-1, and improves endothelial dysfunction in 11\u03b2-HSD inhibitor\u2013induced hypertension and may emerge as a novel therapeutic approach in cardiovascular disease associated with reduced 11\u03b2-HSD activity.\n                  <\/jats:p>","DOI":"10.1161\/01.cir.103.25.3129","type":"journal-article","created":{"date-parts":[[2012,6,11]],"date-time":"2012-06-11T20:09:32Z","timestamp":1339445372000},"page":"3129-3135","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":39,"title":["Endothelin 1 Type A Receptor Antagonism Prevents Vascular Dysfunction and Hypertension Induced by 11\u03b2-Hydroxysteroid Dehydrogenase Inhibition"],"prefix":"10.1161","volume":"103","author":[{"given":"Frank","family":"Ruschitzka","sequence":"first","affiliation":[{"name":"From Cardiology (F.R., T.Q., G.N., F.E., D.H., T.F.L.), Cardiovascular Research and Institute of Physiology, University Hospital Zu\u0308rich, Zu\u0308rich, Switzerland; Department of Endocrinology and Diabetology (A.dG., M.R.), University Hospital Geneva, Geneva, Switzerland; and Department of Clinical Research (S.G.S.), University Hospital Bern, Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Quaschning","sequence":"additional","affiliation":[{"name":"From Cardiology (F.R., T.Q., G.N., F.E., D.H., T.F.L.), Cardiovascular Research and Institute of Physiology, University Hospital Zu\u0308rich, Zu\u0308rich, Switzerland; Department of Endocrinology and Diabetology (A.dG., M.R.), University Hospital Geneva, Geneva, Switzerland; and Department of Clinical Research (S.G.S.), University Hospital Bern, Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Noll","sequence":"additional","affiliation":[{"name":"From Cardiology (F.R., T.Q., G.N., F.E., D.H., T.F.L.), Cardiovascular Research and Institute of Physiology, University Hospital Zu\u0308rich, Zu\u0308rich, Switzerland; Department of Endocrinology and Diabetology (A.dG., M.R.), University Hospital Geneva, Geneva, Switzerland; and Department of Clinical Research (S.G.S.), University Hospital Bern, Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"deGottardi","sequence":"additional","affiliation":[{"name":"From Cardiology (F.R., T.Q., G.N., F.E., D.H., T.F.L.), Cardiovascular Research and Institute of Physiology, University Hospital Zu\u0308rich, Zu\u0308rich, Switzerland; Department of Endocrinology and Diabetology (A.dG., M.R.), University Hospital Geneva, Geneva, Switzerland; and Department of Clinical Research (S.G.S.), University Hospital Bern, Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel F.","family":"Rossier","sequence":"additional","affiliation":[{"name":"From Cardiology (F.R., T.Q., G.N., F.E., D.H., T.F.L.), Cardiovascular Research and Institute of Physiology, University Hospital Zu\u0308rich, Zu\u0308rich, Switzerland; Department of Endocrinology and Diabetology (A.dG., M.R.), University Hospital Geneva, Geneva, Switzerland; and Department of Clinical Research (S.G.S.), University Hospital Bern, Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Enseleit","sequence":"additional","affiliation":[{"name":"From Cardiology (F.R., T.Q., G.N., F.E., D.H., T.F.L.), Cardiovascular Research and Institute of Physiology, University Hospital Zu\u0308rich, Zu\u0308rich, Switzerland; Department of Endocrinology and Diabetology (A.dG., M.R.), University Hospital Geneva, Geneva, Switzerland; and Department of Clinical Research (S.G.S.), University Hospital Bern, Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hu\u0308rlimann","sequence":"additional","affiliation":[{"name":"From Cardiology (F.R., T.Q., G.N., F.E., D.H., T.F.L.), Cardiovascular Research and Institute of Physiology, University Hospital Zu\u0308rich, Zu\u0308rich, Switzerland; Department of Endocrinology and Diabetology (A.dG., M.R.), University Hospital Geneva, Geneva, Switzerland; and Department of Clinical Research (S.G.S.), University Hospital Bern, Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas F.","family":"Lu\u0308scher","sequence":"additional","affiliation":[{"name":"From Cardiology (F.R., T.Q., G.N., F.E., D.H., T.F.L.), Cardiovascular Research and Institute of Physiology, University Hospital Zu\u0308rich, Zu\u0308rich, Switzerland; Department of Endocrinology and Diabetology (A.dG., M.R.), University Hospital Geneva, Geneva, Switzerland; and Department of Clinical Research (S.G.S.), University Hospital Bern, Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidney G.","family":"Shaw","sequence":"additional","affiliation":[{"name":"From Cardiology (F.R., T.Q., G.N., F.E., D.H., T.F.L.), Cardiovascular Research and Institute of Physiology, University Hospital Zu\u0308rich, Zu\u0308rich, Switzerland; Department of Endocrinology and Diabetology (A.dG., M.R.), University Hospital Geneva, Geneva, Switzerland; and Department of Clinical Research (S.G.S.), University Hospital Bern, Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/355262a0"},{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113592"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0895-394"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.1998.tb02301.x"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.25.1.67"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.33.5.1179"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.31.1.459"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.93.5.866"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.21.6.929"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/332411a0"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.31.1.499"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)42066-2"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/333664a0"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.33.4.1013"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)92827-4"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.1.9.649"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199715010-00005"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114477"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/348730a0"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199803193381202"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.3109\/10641969509037425"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.102.10.1086"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1999.4451"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.21.11609"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.47.1.7379260"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199110243251706"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.34.4.876"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)41966-7"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-200018030-00006"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3468(00)90010-1"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.100.16.1680"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118092"},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.7394"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1994.tb14767.x"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.96.5.1593"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(99)00110-8"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1999.0963"},{"key":"e_1_3_1_38_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909023411009"},{"key":"e_1_3_1_39_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909023411001"}],"updated-by":[{"DOI":"10.1161\/circ.104.10.1208","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2001,9,4]],"date-time":"2001-09-04T00:00:00Z","timestamp":999561600000}}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.CIR.103.25.3129","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T09:18:57Z","timestamp":1715505537000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.CIR.103.25.3129"}},"subtitle":["Role of Nitric Oxide"],"short-title":[],"issued":{"date-parts":[[2001,6,26]]},"references-count":39,"journal-issue":{"issue":"25","published-print":{"date-parts":[[2001,6,26]]}},"alternative-id":["10.1161\/01.CIR.103.25.3129"],"URL":"https:\/\/doi.org\/10.1161\/01.cir.103.25.3129","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,6,26]]},"assertion":[{"value":"2000-12-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-02-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-06-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}