{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T03:32:04Z","timestamp":1771644724903,"version":"3.50.1"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[1995,7]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            The transgenic (TG) rat (mREN2)27 is characterized by overexpression of the additional mouse Ren-2\n            <jats:sup>d<\/jats:sup>\n            gene in the adrenal cortex with marked suppression of renal renin. We have previously shown that in salt-depleted TG rats enhanced activation of mineralocorticoid biosynthesis is associated with selective stimulation of adrenal renin. To investigate whether the local renin-angiotensin system regulates aldosterone biosynthesis in the adrenal cortex of TG rats, we studied the effects of the AT\n            <jats:sub>1<\/jats:sub>\n            \u2013angiotensin subtype receptor antagonist DuP 753 on aldosterone production in 5-week-old TG rats during salt restriction. All the rats (n=56) were shifted from regular chow to a diet containing only 0.04% NaCl for 1 week. The AT\n            <jats:sub>1<\/jats:sub>\n            -receptor antagonist DuP 753 (10 mg\/kg per day in drinking water) was administered to 27 of these rats during low-salt diet. Subgroups of rats were killed at 0, 4, and 7 days. Low-salt diet increased both adrenal renin activity (from 31\u00b13 to 77\u00b14 and 85\u00b12 ng angiotensin I \u00b7 h\n            <jats:sup>\u22121<\/jats:sup>\n            \u00b7 mg protein\n            <jats:sup>\u22121<\/jats:sup>\n            at 4 and 7 days, respectively;\n            <jats:italic>P<\/jats:italic>\n            &lt;.001) and mRNA (by 68.4\u00b110% and 80\u00b117% from baseline,\n            <jats:italic>P<\/jats:italic>\n            &lt;.05). In addition, salt restriction was associated with increases of AT\n            <jats:sub>1<\/jats:sub>\n            -receptor subtype mRNA, aldosterone-synthase cytochrome P450 mRNA (by 130\u00b156% and 227\u00b133% at 4 and 7 days, respectively;\n            <jats:italic>P<\/jats:italic>\n            &lt;.05), and plasma aldosterone (from 184\u00b133 to 402\u00b179 and 338\u00b159 pg\/mL,\n            <jats:italic>P<\/jats:italic>\n            &lt;.05), whereas renal renin activity did not change, renin mRNA levels remained almost undetectable, and plasma renin activity showed a transient increase. In contrast, in TG rats treated with DuP 753 salt restriction was associated with increases of renal renin mRNA and renal and plasma renin activity, whereas the stimulation of aldosterone-synthase mRNA was markedly attenuated, and plasma aldosterone did not change. Separate analysis of mouse transgene and endogenous rat renin performed by RNase protection assay in 18 additional TG rats and in 18 age- and sex-matched Sprague-Dawley rats showed that the mouse transgene was prominently expressed in the adrenal glands of TG rats in all experimental conditions. In conclusion, our data show that AT\n            <jats:sub>1<\/jats:sub>\n            -receptor antagonism abolishes the adrenal renin\u2013related stimulation of the aldosterone biosynthesis produced by salt restriction in TG rats. This indicates that in this model the adrenal renin-angiotensin system regulates the mineralocorticoid production via the AT\n            <jats:sub>1<\/jats:sub>\n            -receptor subtype.\n          <\/jats:p>","DOI":"10.1161\/01.res.77.1.73","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:47:05Z","timestamp":1339462025000},"page":"73-79","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Regulation of Aldosterone Biosynthesis by Adrenal Renin Is Mediated Through AT\n            <sub>1<\/sub>\n            Receptors in Renin Transgenic Rats"],"prefix":"10.1161","volume":"77","author":[{"given":"Massimo","family":"Volpe","sequence":"first","affiliation":[{"name":"From the Departments of Internal Medicine (M.V., S.R., B.G., R.R., M.R., I.E., B.T.) and Cellular and Molecular Pathology (A.P.), School of Medicine, Federico II University, Napoli, Italy; Max-Delbru\u0308ck Centrum (D.G.), Berlin-Buch, Germany; and the Cardiovascular Division, Department of Cardiology, Children\u2019s Hospital, Harvard Medical School, Boston, Mass (S.R., M.L.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Speranza","family":"Rubattu","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (M.V., S.R., B.G., R.R., M.R., I.E., B.T.) and Cellular and Molecular Pathology (A.P.), School of Medicine, Federico II University, Napoli, Italy; Max-Delbru\u0308ck Centrum (D.G.), Berlin-Buch, Germany; and the Cardiovascular Division, Department of Cardiology, Children\u2019s Hospital, Harvard Medical School, Boston, Mass (S.R., M.L.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruna","family":"Gigante","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (M.V., S.R., B.G., R.R., M.R., I.E., B.T.) and Cellular and Molecular Pathology (A.P.), School of Medicine, Federico II University, Napoli, Italy; Max-Delbru\u0308ck Centrum (D.G.), Berlin-Buch, Germany; and the Cardiovascular Division, Department of Cardiology, Children\u2019s Hospital, Harvard Medical School, Boston, Mass (S.R., M.L.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Detlev","family":"Ganten","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (M.V., S.R., B.G., R.R., M.R., I.E., B.T.) and Cellular and Molecular Pathology (A.P.), School of Medicine, Federico II University, Napoli, Italy; Max-Delbru\u0308ck Centrum (D.G.), Berlin-Buch, Germany; and the Cardiovascular Division, Department of Cardiology, Children\u2019s Hospital, Harvard Medical School, Boston, Mass (S.R., M.L.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Porcellini","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (M.V., S.R., B.G., R.R., M.R., I.E., B.T.) and Cellular and Molecular Pathology (A.P.), School of Medicine, Federico II University, Napoli, Italy; Max-Delbru\u0308ck Centrum (D.G.), Berlin-Buch, Germany; and the Cardiovascular Division, Department of Cardiology, Children\u2019s Hospital, Harvard Medical School, Boston, Mass (S.R., M.L.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosaria","family":"Russo","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (M.V., S.R., B.G., R.R., M.R., I.E., B.T.) and Cellular and Molecular Pathology (A.P.), School of Medicine, Federico II University, Napoli, Italy; Max-Delbru\u0308ck Centrum (D.G.), Berlin-Buch, Germany; and the Cardiovascular Division, Department of Cardiology, Children\u2019s Hospital, Harvard Medical School, Boston, Mass (S.R., M.L.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Romano","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (M.V., S.R., B.G., R.R., M.R., I.E., B.T.) and Cellular and Molecular Pathology (A.P.), School of Medicine, Federico II University, Napoli, Italy; Max-Delbru\u0308ck Centrum (D.G.), Berlin-Buch, Germany; and the Cardiovascular Division, Department of Cardiology, Children\u2019s Hospital, Harvard Medical School, Boston, Mass (S.R., M.L.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iolanda","family":"Enea","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (M.V., S.R., B.G., R.R., M.R., I.E., B.T.) and Cellular and Molecular Pathology (A.P.), School of Medicine, Federico II University, Napoli, Italy; Max-Delbru\u0308ck Centrum (D.G.), Berlin-Buch, Germany; and the Cardiovascular Division, Department of Cardiology, Children\u2019s Hospital, Harvard Medical School, Boston, Mass (S.R., M.L.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min Ae","family":"Lee","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (M.V., S.R., B.G., R.R., M.R., I.E., B.T.) and Cellular and Molecular Pathology (A.P.), School of Medicine, Federico II University, Napoli, Italy; Max-Delbru\u0308ck Centrum (D.G.), Berlin-Buch, Germany; and the Cardiovascular Division, Department of Cardiology, Children\u2019s Hospital, Harvard Medical School, Boston, Mass (S.R., M.L.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Trimarco","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (M.V., S.R., B.G., R.R., M.R., I.E., B.T.) and Cellular and Molecular Pathology (A.P.), School of Medicine, Federico II University, Napoli, Italy; Max-Delbru\u0308ck Centrum (D.G.), Berlin-Buch, Germany; and the Cardiovascular Division, Department of Cardiology, Children\u2019s Hospital, Harvard Medical School, Boston, Mass (S.R., M.L.)."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_1_1_2","doi-asserted-by":"crossref","unstructured":"Mulrow PJ. The adrenal cortical renin-angiotensin system. In: Robertson JJS Nicholls MJ eds. The Renin-Angiotensin System. London England: R Gower Medical Publishing; 1993:44.1-44.9.","DOI":"10.1097\/00041552-199301000-00006"},{"key":"e_1_3_1_2_2","doi-asserted-by":"crossref","unstructured":"Doi Y Atarashi K Franco-Saenz R Mulrow PJ. Effects of changes in sodium or potassium balance and nephrectomy on adrenal renin and aldosterone concentrations. Hypertension. 1984;6(suppl I):I-124-I-129.","DOI":"10.1161\/01.HYP.6.2_Pt_2.I124"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/344541a0"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1992.4"},{"key":"e_1_3_1_5_2","first-page":"807","volume":"131","year":"1992","unstructured":"Sander M, Bader M, Djavidani B, Maser-Gluth C, Vecsei P, Mullins J, Ganten D, Peters J. The role of the adrenal gland in hypertensive transgenic rat TGR (mREN2)27. Endocrinology. 1992;131:807-814.","journal-title":"Endocrinology"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1994.267.4.E515"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.16.6.635"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.19.3.263"},{"key":"e_1_3_1_9_2","first-page":"33","volume":"1","year":"1990","unstructured":"Chiu AT, McCall DE, Ardecky RS, Duncia JV, Nguyen TT, Timmermans PBMWM. Angiotensin II receptor subtypes and their selective non peptide ligands. Receptor. 1990;1:33-40.","journal-title":"Receptor"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/4.3.288"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199308000-00005"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.23.4.422"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199106000-00008"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.130.6.1597135"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.1.148"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplegacy.1974.227.1.224"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-107-1-55"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/289507a0"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-124-6-2907"},{"key":"e_1_3_1_21_2","doi-asserted-by":"crossref","unstructured":"Herblin WF Chiu AT McCall DE Ardecky RJ Carini DJ Duncia JV Pease LJ Wong PC Wexler RR Johnson AL Timmermans PBMWM. Angiotensin II receptor heterogeneity. Am J Hypertens. 1991;4(pt 2):299S-302S.","DOI":"10.1093\/ajh\/4.4.299S"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.32.040192.001031"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-196-43175"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.134.6.8194463"},{"key":"e_1_3_1_25_2","doi-asserted-by":"crossref","unstructured":"Gupta P Yamaguchi T Franco-Saenz R Mulrow PJ. Locally generated angiotensin II in the adrenal gland regulates basal ACTH and potassium stimulated aldosterone secretion. J Hypertens. 1994;12(suppl 3):S133. Abstract.","DOI":"10.1161\/01.HYP.25.3.443"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116292"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/5.12.221S"},{"key":"e_1_3_1_28_2","unstructured":"Tokita Y Franco-Saenz R Reimann E Mulrow PJ. Differential expression of mouse and rat renin in the transgenic rat: alteration by an ACE inhibitor. J Hypertens. 1994;12(suppl 3):S150. Abstract."}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.RES.77.1.73","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T20:24:02Z","timestamp":1715545442000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.RES.77.1.73"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,7]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1995,7]]}},"alternative-id":["10.1161\/01.RES.77.1.73"],"URL":"https:\/\/doi.org\/10.1161\/01.res.77.1.73","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,7]]},"assertion":[{"value":"1994-07-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1995-03-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1995-07-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}