{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:47:30Z","timestamp":1787017650123,"version":"build-2736575974"},"reference-count":61,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2008,2]]},"abstract":"\n Aldosterone acts upon mineralocorticoid receptors in the brain to increase blood pressure and sympathetic nerve activity, but the mechanisms are still poorly understood. We hypothesized that aldosterone increases sympathetic nerve activity by upregulating the renin-angiotensin system (RAS) and oxidative stress in the brain, as it does in peripheral tissues. In Sprague-Dawley rats, aldosterone (Aldo) or vehicle (Veh) was infused for 1 wk via an intracerebroventricular (ICV) cannula, while RU-28318 (selective mineralocorticoid receptor antagonist), Tempol (superoxide dismutase mimetic), losartan [angiotensin II type 1 receptor (AT\n 1<\/jats:sub>\n R) antagonist], or Veh was infused simultaneously via a second ICV cannula. After 1 wk of ICV Aldo, plasma norepinephrine was increased and mean arterial pressure was slightly elevated, but heart rate was unchanged. These effects were ameliorated by ICV infusion of RU-28318, Tempol or losartan. Aldo increased expression of AT\n 1<\/jats:sub>\n R and angiotensin-converting enzyme (ACE) mRNA in hypothalamic tissue. RU-28318 minimized and Tempol prevented the increase in AT\n 1<\/jats:sub>\n R mRNA; RU-28318 prevented the increase in ACE mRNA. Losartan had no effect on AT\n 1<\/jats:sub>\n R or ACE mRNA. Immunohistochemistry revealed Aldo-induced increases in dihydroethidium staining (indicating oxidative stress) and Fra-like activity (indicating neuronal excitation) in neurons of the hypothalamic paraventricular nucleus (PVN). RU-28318 prevented the increases in superoxide and Fra-like activity in PVN; Tempol and losartan minimized these effects. Acute ICV infusions of sarthran (AT\n 1<\/jats:sub>\n R antagonist) or Tempol produced greater sympathoinhibition in Aldo-treated than in Veh-treated rats. Thus aldosterone upregulates key elements of brain RAS and induces oxidative stress in the hypothalamus. Aldosterone may increase sympathetic nerve activity by these mechanisms.\n <\/jats:p>","DOI":"10.1152\/ajpheart.01131.2007","type":"journal-article","created":{"date-parts":[[2007,12,27]],"date-time":"2007-12-27T20:34:04Z","timestamp":1198787644000},"page":"H1067-H1074","source":"Crossref","is-referenced-by-count":104,"title":["Aldosterone acts centrally to increase brain renin-angiotensin system activity and oxidative stress in normal rats"],"prefix":"10.1152","volume":"294","author":[{"given":"Zhi-Hua","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ming","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun-Guang","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B.","family":"Felder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00279.2002"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00963982"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000176588.51027.35"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000154365.30593.d3"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000179088.57586.26"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00619.2003"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00052.2005"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00190.2003"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1019185"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00393.2002"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.521625"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01072.2003"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1210\/endo.137.12.8940344"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000168056.66981.c2"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000146676.04359.64"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1006\/frne.1997.0157"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00355.2004"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1990.258.3.E482"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1990.258.4.E649"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1016\/0039-128X(96)00010-4"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-198806000-00002"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.104.2.137"},{"key":"R23","doi-asserted-by":"crossref","unstructured":"Hendler NH\n , Livingston A.\n The localization over time of exogenous aldosterone and angiotensin II in various organs.\n Pavlov J Biol Sci\n 13\n : 187\u2013193, 1978.","DOI":"10.1007\/BF03001394"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-1157"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00024.2006"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00651.2004"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2006.8.1583"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000244092.95152.86"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00255.2003"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000112964.40701.93"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1042\/CS20070123"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1989.256.2.R371"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000203772.78696.67"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000256955.74461.93"},{"key":"R35","unstructured":"Paxinos G\n , Watson C.\n The Rat Brain Is Stereotaxic Coordinates.\n Sydney, Australia: Academic, 1986."},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-006-0056-1"},{"key":"R37","doi-asserted-by":"crossref","unstructured":"Peysner K\n , Henry CA, Malvin RL.\n Central infusion of aldosterone increases blood pressure by mechanisms independent of Na retention.\n Clin Exp Hypertens A\n 12\n : 399\u2013414, 1990.","DOI":"10.3109\/10641969009074742"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.33.4.981"},{"key":"R39","unstructured":"Roizen MF\n , Moss J, Henry DP, Weise V, Kopin IJ.\n Effect of general anesthetics on handling- and decapitation-induced increases in sympathoadrenal discharge.\n J Pharmacol Exp Ther\n 204\n : 11\u201318, 1978."},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31242"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-005-0088-y"},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1139\/y85-250"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000049621.85474.CF"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00051.2004"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-1674"},{"key":"R46","unstructured":"Sun Y\n , Weber KT.\n Angiotensin II and aldosterone receptor binding in rat heart and kidney: response to chronic angiotensin II or aldosterone administration.\n J Lab Clin Med\n 122\n : 404\u2013411, 1993."},{"key":"R47","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-879X2004000800018"},{"key":"R48","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2826.2002.00836.x"},{"key":"R49","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00299.2003"},{"key":"R50","doi-asserted-by":"publisher","DOI":"10.1054\/jcaf.2002.125369"},{"key":"R51","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000257356.20527.c5"},{"key":"R52","unstructured":"Yu Y\n , Wei SG, Zhang ZH, Gomez-Sanchez EP, Weiss RM, Felder RB.\n Does aldosterone upregulate the brain renin-angiotensin system in rats with heart failure.\n Hypertension.\n In press."},{"key":"R53","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.148940"},{"key":"R54","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00504.2003"},{"key":"R55","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000224296.96235.dd"},{"key":"R56","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00406.2002"},{"key":"R57","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-200101000-00012"},{"key":"R58","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000043501.47934.FA"},{"key":"R59","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000246614.47231.25"},{"key":"R60","unstructured":"Zucker IH\n , Pliquett RU.\n Novel mechanisms of sympatho-excitation in chronic heart failure.\n Heart Fail Monit\n 3\n : 2\u20137, 2002."},{"key":"R61","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2001.tb03696.x"}],"container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpheart.01131.2007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T09:37:37Z","timestamp":1684143457000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpheart.01131.2007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,2]]},"references-count":61,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2008,2]]}},"alternative-id":["10.1152\/ajpheart.01131.2007"],"URL":"https:\/\/doi.org\/10.1152\/ajpheart.01131.2007","relation":{},"ISSN":["0363-6135","1522-1539"],"issn-type":[{"value":"0363-6135","type":"print"},{"value":"1522-1539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,2]]}}}