{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:56:20Z","timestamp":1791107780222,"version":"4.1.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"23","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2005,6,14]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background\u2014<\/jats:italic>\n            <\/jats:bold>\n            Aldosterone and angiotensin (Ang) II both may cause organ damage. Circulating aldosterone is produced in the adrenals; however, local cardiac synthesis has been reported. Aldosterone concentrations depend on the activity of aldosterone synthase (CYP11B2). We tested the hypothesis that reducing aldosterone by inhibiting CYP11B2 or by adrenalectomy (ADX) may ameliorate organ damage. Furthermore, we investigated how much local cardiac aldosterone originates from the adrenal gland.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            We investigated the effect of the CYP11B2 inhibitor FAD286, losartan, and the consequences of ADX in transgenic rats overexpressing both the human renin and angiotensinogen genes (dTGR). dTGR-ADX received dexamethasone and 1% salt. Dexamethasone-treated dTGR-salt served as a control group in the ADX protocol. Untreated dTGR developed hypertension and cardiac and renal damage and had a 40% mortality rate (5\/13) at 7 weeks. FAD286 reduced mortality to 10% (1\/10) and ameliorated cardiac hypertrophy, albuminuria, cell infiltration, and matrix deposition in the heart and kidney. FAD286 had no effect on blood pressure at weeks 5 and 6 but slightly reduced blood pressure at week7 (177\u00b16 mm Hg in dTGR+FAD286 and 200\u00b15 mm Hg in dTGR). Losartan normalized blood pressure during the entire study. Circulating and cardiac aldosterone levels were reduced in FAD286 or losartan-treated dTGR. ADX combined with dexamethasone and salt treatment decreased circulating and cardiac aldosterone to barely detectable levels. At week 7, ADX-dTGR-dexamethasone-salt had a 22% mortality rate compared with 73% in dTGR-dexamethasone-salt. Both groups were similarly hypertensive (190\u00b19 and 187\u00b14 mm Hg). In contrast, cardiac hypertrophy index, albuminuria, cell infiltration, and matrix deposition were significantly reduced after ADX (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05).\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            Aldosterone plays a key role in the pathogenesis of Ang II\u2013induced organ damage. Both FAD286 and ADX reduced circulating and cardiac aldosterone levels. The present results show that aldosterone produced in the adrenals is the main source of cardiac aldosterone.\n          <\/jats:p>","DOI":"10.1161\/circulationaha.104.521625","type":"journal-article","created":{"date-parts":[[2005,6,7]],"date-time":"2005-06-07T00:25:45Z","timestamp":1118103945000},"page":"3087-3094","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":155,"title":["Aldosterone Synthase Inhibitor Ameliorates Angiotensin II\u2013Induced Organ Damage"],"prefix":"10.1161","volume":"111","author":[{"given":"Anette","family":"Fiebeler","sequence":"first","affiliation":[{"name":"From the Medical Faculty of the Charite\u0301 (A.F., E.S., G.H., N.A.-S., R.D., M.W., S.M., F.C.L., D.N.M.), HELIOS Klinikum-Berlin, Franz Volhard Clinic, Berlin, Germany; Max Delbru\u0308ck Center for Molecular Medicine (F.C.L., D.N.M.), Berlin-Buch, Germany; Medical School of Hannover (S.R.), Hannover, Germany; Novartis Institutes for Biomedical Research (A.Y.J., R.L.W.), East Hanover, NJ; Centre Hospitalier Universitaire Vaudois (J.N.), Hypertension Division, Lausanne, Switzerland; and University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju\u0308rg","family":"Nussberger","sequence":"additional","affiliation":[{"name":"From the Medical Faculty of the Charite\u0301 (A.F., E.S., G.H., N.A.-S., R.D., M.W., S.M., F.C.L., D.N.M.), HELIOS Klinikum-Berlin, Franz Volhard Clinic, Berlin, Germany; Max Delbru\u0308ck Center for Molecular Medicine (F.C.L., D.N.M.), Berlin-Buch, Germany; Medical School of Hannover (S.R.), Hannover, Germany; Novartis Institutes for Biomedical Research (A.Y.J., R.L.W.), East Hanover, NJ; Centre Hospitalier Universitaire Vaudois (J.N.), Hypertension Division, Lausanne, Switzerland; and University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erdenechimeg","family":"Shagdarsuren","sequence":"additional","affiliation":[{"name":"From the Medical Faculty of the Charite\u0301 (A.F., E.S., G.H., N.A.-S., R.D., M.W., S.M., F.C.L., D.N.M.), HELIOS Klinikum-Berlin, Franz Volhard Clinic, Berlin, Germany; Max Delbru\u0308ck Center for Molecular Medicine (F.C.L., D.N.M.), Berlin-Buch, Germany; Medical School of Hannover (S.R.), Hannover, Germany; Novartis Institutes for Biomedical Research (A.Y.J., R.L.W.), East Hanover, NJ; Centre Hospitalier Universitaire Vaudois (J.N.), Hypertension Division, Lausanne, Switzerland; and University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Rong","sequence":"additional","affiliation":[{"name":"From the Medical Faculty of the Charite\u0301 (A.F., E.S., G.H., N.A.-S., R.D., M.W., S.M., F.C.L., D.N.M.), HELIOS Klinikum-Berlin, Franz Volhard Clinic, Berlin, Germany; Max Delbru\u0308ck Center for Molecular Medicine (F.C.L., D.N.M.), Berlin-Buch, Germany; Medical School of Hannover (S.R.), Hannover, Germany; Novartis Institutes for Biomedical Research (A.Y.J., R.L.W.), East Hanover, NJ; Centre Hospitalier Universitaire Vaudois (J.N.), Hypertension Division, Lausanne, Switzerland; and University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Hilfenhaus","sequence":"additional","affiliation":[{"name":"From the Medical Faculty of the Charite\u0301 (A.F., E.S., G.H., N.A.-S., R.D., M.W., S.M., F.C.L., D.N.M.), HELIOS Klinikum-Berlin, Franz Volhard Clinic, Berlin, Germany; Max Delbru\u0308ck Center for Molecular Medicine (F.C.L., D.N.M.), Berlin-Buch, Germany; Medical School of Hannover (S.R.), Hannover, Germany; Novartis Institutes for Biomedical Research (A.Y.J., R.L.W.), East Hanover, NJ; Centre Hospitalier Universitaire Vaudois (J.N.), Hypertension Division, Lausanne, Switzerland; and University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidal","family":"Al-Saadi","sequence":"additional","affiliation":[{"name":"From the Medical Faculty of the Charite\u0301 (A.F., E.S., G.H., N.A.-S., R.D., M.W., S.M., F.C.L., D.N.M.), HELIOS Klinikum-Berlin, Franz Volhard Clinic, Berlin, Germany; Max Delbru\u0308ck Center for Molecular Medicine (F.C.L., D.N.M.), Berlin-Buch, Germany; Medical School of Hannover (S.R.), Hannover, Germany; Novartis Institutes for Biomedical Research (A.Y.J., R.L.W.), East Hanover, NJ; Centre Hospitalier Universitaire Vaudois (J.N.), Hypertension Division, Lausanne, Switzerland; and University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Dechend","sequence":"additional","affiliation":[{"name":"From the Medical Faculty of the Charite\u0301 (A.F., E.S., G.H., N.A.-S., R.D., M.W., S.M., F.C.L., D.N.M.), HELIOS Klinikum-Berlin, Franz Volhard Clinic, Berlin, Germany; Max Delbru\u0308ck Center for Molecular Medicine (F.C.L., D.N.M.), Berlin-Buch, Germany; Medical School of Hannover (S.R.), Hannover, Germany; Novartis Institutes for Biomedical Research (A.Y.J., R.L.W.), East Hanover, NJ; Centre Hospitalier Universitaire Vaudois (J.N.), Hypertension Division, Lausanne, Switzerland; and University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maren","family":"Wellner","sequence":"additional","affiliation":[{"name":"From the Medical Faculty of the Charite\u0301 (A.F., E.S., G.H., N.A.-S., R.D., M.W., S.M., F.C.L., D.N.M.), HELIOS Klinikum-Berlin, Franz Volhard Clinic, Berlin, Germany; Max Delbru\u0308ck Center for Molecular Medicine (F.C.L., D.N.M.), Berlin-Buch, Germany; Medical School of Hannover (S.R.), Hannover, Germany; Novartis Institutes for Biomedical Research (A.Y.J., R.L.W.), East Hanover, NJ; Centre Hospitalier Universitaire Vaudois (J.N.), Hypertension Division, Lausanne, Switzerland; and University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Meiners","sequence":"additional","affiliation":[{"name":"From the Medical Faculty of the Charite\u0301 (A.F., E.S., G.H., N.A.-S., R.D., M.W., S.M., F.C.L., D.N.M.), HELIOS Klinikum-Berlin, Franz Volhard Clinic, Berlin, Germany; Max Delbru\u0308ck Center for Molecular Medicine (F.C.L., D.N.M.), Berlin-Buch, Germany; Medical School of Hannover (S.R.), Hannover, Germany; Novartis Institutes for Biomedical Research (A.Y.J., R.L.W.), East Hanover, NJ; Centre Hospitalier Universitaire Vaudois (J.N.), Hypertension Division, Lausanne, Switzerland; and University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Maser-Gluth","sequence":"additional","affiliation":[{"name":"From the Medical Faculty of the Charite\u0301 (A.F., E.S., G.H., N.A.-S., R.D., M.W., S.M., F.C.L., D.N.M.), HELIOS Klinikum-Berlin, Franz Volhard Clinic, Berlin, Germany; Max Delbru\u0308ck Center for Molecular Medicine (F.C.L., D.N.M.), Berlin-Buch, Germany; Medical School of Hannover (S.R.), Hannover, Germany; Novartis Institutes for Biomedical Research (A.Y.J., R.L.W.), East Hanover, NJ; Centre Hospitalier Universitaire Vaudois (J.N.), Hypertension Division, Lausanne, Switzerland; and University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arco Y.","family":"Jeng","sequence":"additional","affiliation":[{"name":"From the Medical Faculty of the Charite\u0301 (A.F., E.S., G.H., N.A.-S., R.D., M.W., S.M., F.C.L., D.N.M.), HELIOS Klinikum-Berlin, Franz Volhard Clinic, Berlin, Germany; Max Delbru\u0308ck Center for Molecular Medicine (F.C.L., D.N.M.), Berlin-Buch, Germany; Medical School of Hannover (S.R.), Hannover, Germany; Novartis Institutes for Biomedical Research (A.Y.J., R.L.W.), East Hanover, NJ; Centre Hospitalier Universitaire Vaudois (J.N.), Hypertension Division, Lausanne, Switzerland; and University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randy L.","family":"Webb","sequence":"additional","affiliation":[{"name":"From the Medical Faculty of the Charite\u0301 (A.F., E.S., G.H., N.A.-S., R.D., M.W., S.M., F.C.L., D.N.M.), HELIOS Klinikum-Berlin, Franz Volhard Clinic, Berlin, Germany; Max Delbru\u0308ck Center for Molecular Medicine (F.C.L., D.N.M.), Berlin-Buch, Germany; Medical School of Hannover (S.R.), Hannover, Germany; Novartis Institutes for Biomedical Research (A.Y.J., R.L.W.), East Hanover, NJ; Centre Hospitalier Universitaire Vaudois (J.N.), Hypertension Division, Lausanne, Switzerland; and University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich C.","family":"Luft","sequence":"additional","affiliation":[{"name":"From the Medical Faculty of the Charite\u0301 (A.F., E.S., G.H., N.A.-S., R.D., M.W., S.M., F.C.L., D.N.M.), HELIOS Klinikum-Berlin, Franz Volhard Clinic, Berlin, Germany; Max Delbru\u0308ck Center for Molecular Medicine (F.C.L., D.N.M.), Berlin-Buch, Germany; Medical School of Hannover (S.R.), Hannover, Germany; Novartis Institutes for Biomedical Research (A.Y.J., R.L.W.), East Hanover, NJ; Centre Hospitalier Universitaire Vaudois (J.N.), Hypertension Division, Lausanne, Switzerland; and University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik N.","family":"Muller","sequence":"additional","affiliation":[{"name":"From the Medical Faculty of the Charite\u0301 (A.F., E.S., G.H., N.A.-S., R.D., M.W., S.M., F.C.L., D.N.M.), HELIOS Klinikum-Berlin, Franz Volhard Clinic, Berlin, Germany; Max Delbru\u0308ck Center for Molecular Medicine (F.C.L., D.N.M.), Berlin-Buch, Germany; Medical School of Hannover (S.R.), Hannover, Germany; Novartis Institutes for Biomedical Research (A.Y.J., R.L.W.), East Hanover, NJ; Centre Hospitalier Universitaire Vaudois (J.N.), Hypertension Division, Lausanne, Switzerland; and University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909023411001"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa030207"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2003.10.012"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/147323000102900103"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.0000044937.95080.e9"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000068340.96506.0f"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64445-8"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.33.1.212"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000131860.80444.ab"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.37.2.787"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.16.7806"},{"key":"e_1_3_3_12_2","first-page":"789","volume":"104","year":"1984","unstructured":"Nussberger J, Waeber B, Brunner HR, Burris JF, Vetter W. 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Transcardiac gradient of aldosterone before and after spironolactone in patients with congestive heart failure. 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