{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:08:21Z","timestamp":1790755701023,"version":"4.1.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>The comorbidity of excess salt and elevated plasma aldosterone has deleterious effects in cardiovascular disease. We evaluated the mechanisms behind the paradoxical increase in aldosterone biosynthesis in relation to dietary intake of salt.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Dahl salt-sensitive (Dahl-S) and salt-resistant (Dahl-R) rats were fed a high-salt diet, and plasma and tissue levels of aldosterone in the adrenal gland and heart were quantified by liquid chromatography\u2013electrospray ionization\u2013tandem mass spectrometry. In Dahl-S rats, we found that the delayed and paradoxical increase in aldosterone biosynthesis after the initial and appropriate response to high salt. The late rise in aldosterone biosynthesis was accompanied by upregulation of CYP11B2 expression in the zona glomerulosa and increased adrenal angiotensin II levels and renin-angiotensin system components. It preceded the appearance of left ventricular systolic dysfunction and renal insufficiency. Blockade of angiotensin AT\n              <jats:sub>1<\/jats:sub>\n              receptors reversed the paradoxical increase in aldosterone biosynthesis. In contrast, Dahl-R rats maintained the initial suppression of aldosterone biosynthesis. Aldosterone levels in the heart closely paralleled those in the plasma and adrenal gland and disappeared after bilateral adrenalectomy.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion\u2014<\/jats:title>\n            <jats:p>Chronic salt overload in Dahl-S rats stimulates aberrant aldosterone production via activation of the local renin-angiotensin system in the adrenal gland, thereby creating the comorbidity of excess salt and elevated plasma aldosterone.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.111.242719","type":"journal-article","created":{"date-parts":[[2012,3,3]],"date-time":"2012-03-03T23:03:32Z","timestamp":1330815812000},"page":"1194-1203","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":25,"title":["Biphasic Time Course of the Changes in Aldosterone Biosynthesis Under High-Salt Conditions in Dahl Salt-Sensitive Rats"],"prefix":"10.1161","volume":"32","author":[{"given":"Shintaro","family":"Morizane","sequence":"first","affiliation":[{"name":"From the Department of Cardiology (S.M., K.O., K.I., T.M., Y.K., H.I., X.Y., K.F., M.S.), the Department of Biochemistry and Integrative Medical Biology (F.M.), and the Department of Geriatric Medicine (K.S.), Keio University School of Medicine, Tokyo, Japan; the Division of Basic Biological Sciences, Faculty of Pharmacy, Keio University, Tokyo, Japan (S.M., K.O., T.S.); the Department of Pharmacology, Kagawa Medical University, Kagawa, Japan (A.N.); Aska Pharma Medical Co Ltd, Shimo-sakunobe,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiko","family":"Mitani","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (S.M., K.O., K.I., T.M., Y.K., H.I., X.Y., K.F., M.S.), the Department of Biochemistry and Integrative Medical Biology (F.M.), and the Department of Geriatric Medicine (K.S.), Keio University School of Medicine, Tokyo, Japan; the Division of Basic Biological Sciences, Faculty of Pharmacy, Keio University, Tokyo, Japan (S.M., K.O., T.S.); the Department of Pharmacology, Kagawa Medical University, Kagawa, Japan (A.N.); Aska Pharma Medical Co Ltd, Shimo-sakunobe,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kae","family":"Ozawa","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (S.M., K.O., K.I., T.M., Y.K., H.I., X.Y., K.F., M.S.), the Department of Biochemistry and Integrative Medical Biology (F.M.), and the Department of Geriatric Medicine (K.S.), Keio University School of Medicine, Tokyo, Japan; the Division of Basic Biological Sciences, Faculty of Pharmacy, Keio University, Tokyo, Japan (S.M., K.O., T.S.); the Department of Pharmacology, Kagawa Medical University, Kagawa, Japan (A.N.); Aska Pharma Medical Co Ltd, Shimo-sakunobe,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Ito","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (S.M., K.O., K.I., T.M., Y.K., H.I., X.Y., K.F., M.S.), the Department of Biochemistry and Integrative Medical Biology (F.M.), and the Department of Geriatric Medicine (K.S.), Keio University School of Medicine, Tokyo, Japan; the Division of Basic Biological Sciences, Faculty of Pharmacy, Keio University, Tokyo, Japan (S.M., K.O., T.S.); the Department of Pharmacology, Kagawa Medical University, Kagawa, Japan (A.N.); Aska Pharma Medical Co Ltd, Shimo-sakunobe,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Matsuhashi","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (S.M., K.O., K.I., T.M., Y.K., H.I., X.Y., K.F., M.S.), the Department of Biochemistry and Integrative Medical Biology (F.M.), and the Department of Geriatric Medicine (K.S.), Keio University School of Medicine, Tokyo, Japan; the Division of Basic Biological Sciences, Faculty of Pharmacy, Keio University, Tokyo, Japan (S.M., K.O., T.S.); the Department of Pharmacology, Kagawa Medical University, Kagawa, Japan (A.N.); Aska Pharma Medical Co Ltd, Shimo-sakunobe,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Katsumata","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (S.M., K.O., K.I., T.M., Y.K., H.I., X.Y., K.F., M.S.), the Department of Biochemistry and Integrative Medical Biology (F.M.), and the Department of Geriatric Medicine (K.S.), Keio University School of Medicine, Tokyo, Japan; the Division of Basic Biological Sciences, Faculty of Pharmacy, Keio University, Tokyo, Japan (S.M., K.O., T.S.); the Department of Pharmacology, Kagawa Medical University, Kagawa, Japan (A.N.); Aska Pharma Medical Co Ltd, Shimo-sakunobe,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Ito","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (S.M., K.O., K.I., T.M., Y.K., H.I., X.Y., K.F., M.S.), the Department of Biochemistry and Integrative Medical Biology (F.M.), and the Department of Geriatric Medicine (K.S.), Keio University School of Medicine, Tokyo, Japan; the Division of Basic Biological Sciences, Faculty of Pharmacy, Keio University, Tokyo, Japan (S.M., K.O., T.S.); the Department of Pharmacology, Kagawa Medical University, Kagawa, Japan (A.N.); Aska Pharma Medical Co Ltd, Shimo-sakunobe,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiang","family":"Yan","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (S.M., K.O., K.I., T.M., Y.K., H.I., X.Y., K.F., M.S.), the Department of Biochemistry and Integrative Medical Biology (F.M.), and the Department of Geriatric Medicine (K.S.), Keio University School of Medicine, Tokyo, Japan; the Division of Basic Biological Sciences, Faculty of Pharmacy, Keio University, Tokyo, Japan (S.M., K.O., T.S.); the Department of Pharmacology, Kagawa Medical University, Kagawa, Japan (A.N.); Aska Pharma Medical Co Ltd, Shimo-sakunobe,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Shinmura","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (S.M., K.O., K.I., T.M., Y.K., H.I., X.Y., K.F., M.S.), the Department of Biochemistry and Integrative Medical Biology (F.M.), and the Department of Geriatric Medicine (K.S.), Keio University School of Medicine, Tokyo, Japan; the Division of Basic Biological Sciences, Faculty of Pharmacy, Keio University, Tokyo, Japan (S.M., K.O., T.S.); the Department of Pharmacology, Kagawa Medical University, Kagawa, Japan (A.N.); Aska Pharma Medical Co Ltd, Shimo-sakunobe,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Nishiyama","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (S.M., K.O., K.I., T.M., Y.K., H.I., X.Y., K.F., M.S.), the Department of Biochemistry and Integrative Medical Biology (F.M.), and the Department of Geriatric Medicine (K.S.), Keio University School of Medicine, Tokyo, Japan; the Division of Basic Biological Sciences, Faculty of Pharmacy, Keio University, Tokyo, Japan (S.M., K.O., T.S.); the Department of Pharmacology, Kagawa Medical University, Kagawa, Japan (A.N.); Aska Pharma Medical Co Ltd, Shimo-sakunobe,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seijiro","family":"Honma","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (S.M., K.O., K.I., T.M., Y.K., H.I., X.Y., K.F., M.S.), the Department of Biochemistry and Integrative Medical Biology (F.M.), and the Department of Geriatric Medicine (K.S.), Keio University School of Medicine, Tokyo, Japan; the Division of Basic Biological Sciences, Faculty of Pharmacy, Keio University, Tokyo, Japan (S.M., K.O., T.S.); the Department of Pharmacology, Kagawa Medical University, Kagawa, Japan (A.N.); Aska Pharma Medical Co Ltd, Shimo-sakunobe,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (S.M., K.O., K.I., T.M., Y.K., H.I., X.Y., K.F., M.S.), the Department of Biochemistry and Integrative Medical Biology (F.M.), and the Department of Geriatric Medicine (K.S.), Keio University School of Medicine, Tokyo, Japan; the Division of Basic Biological Sciences, Faculty of Pharmacy, Keio University, Tokyo, Japan (S.M., K.O., T.S.); the Department of Pharmacology, Kagawa Medical University, Kagawa, Japan (A.N.); Aska Pharma Medical Co Ltd, Shimo-sakunobe,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Funder","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (S.M., K.O., K.I., T.M., Y.K., H.I., X.Y., K.F., M.S.), the Department of Biochemistry and Integrative Medical Biology (F.M.), and the Department of Geriatric Medicine (K.S.), Keio University School of Medicine, Tokyo, Japan; the Division of Basic Biological Sciences, Faculty of Pharmacy, Keio University, Tokyo, Japan (S.M., K.O., T.S.); the Department of Pharmacology, Kagawa Medical University, Kagawa, Japan (A.N.); Aska Pharma Medical Co Ltd, Shimo-sakunobe,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichi","family":"Fukuda","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (S.M., K.O., K.I., T.M., Y.K., H.I., X.Y., K.F., M.S.), the Department of Biochemistry and Integrative Medical Biology (F.M.), and the Department of Geriatric Medicine (K.S.), Keio University School of Medicine, Tokyo, Japan; the Division of Basic Biological Sciences, Faculty of Pharmacy, Keio University, Tokyo, Japan (S.M., K.O., T.S.); the Department of Pharmacology, Kagawa Medical University, Kagawa, Japan (A.N.); Aska Pharma Medical Co Ltd, Shimo-sakunobe,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoaki","family":"Sano","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (S.M., K.O., K.I., T.M., Y.K., H.I., X.Y., K.F., M.S.), the Department of Biochemistry and Integrative Medical Biology (F.M.), and the Department of Geriatric Medicine (K.S.), Keio University School of Medicine, Tokyo, Japan; the Division of Basic Biological Sciences, Faculty of Pharmacy, Keio University, Tokyo, Japan (S.M., K.O., T.S.); the Department of Pharmacology, Kagawa Medical University, Kagawa, Japan (A.N.); Aska Pharma Medical Co Ltd, Shimo-sakunobe,..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(80)90002-9"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)05189-1"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-008-0343-1"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-008-0336-0"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.158.3808.1589"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplegacy.1974.227.1.224"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.10.3295"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/344541a0"},{"key":"e_1_3_4_10_2","first-page":"807","article-title":"The role of the adrenal gland in hypertensive transgenic rat tgr(mren2)27.","volume":"131","author":"Sander M","year":"1992","unstructured":"Sander M, Bader M, Djavidani B, Maser-Gluth C, Vecsei P, Mullins J, Ganten D, Peters J. 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