{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T17:42:04Z","timestamp":1770486124284,"version":"3.49.0"},"reference-count":72,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2013,11,21]],"date-time":"2013-11-21T00:00:00Z","timestamp":1384992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>\n<jats:list>\n\n<jats:list-item><jats:p> According to Guyton's model, impaired renal sodium excretion plays a key role in the increased salt sensitivity of blood pressure (<jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content>). Several factors contribute to impaired renal sodium excretion, including the sympathetic nervous system, the renin\u2013angiotensin system and aldosterone. Accumulating evidence suggests that abnormalities in aldosterone and its receptor (i.e. the mineralocorticoid receptor (<jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content>)) are involved in the development of salt\u2010sensitive (<jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>) hypertension.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p> Patients with metabolic syndrome often exhibit hyperaldosteronism and are susceptible to <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content> hypertension. Aldosterone secretion from the adrenal glands is not suppressed in obese hypertensive rats fed a high\u2010salt diet because of the abundant production of adipocyte\u2010derived aldosterone\u2010releasing factors, which are independent of the negative feedback regulation of aldosterone secretion by the renin\u2013angiotensin\u2013aldosterone system. Increased plasma aldosterone levels lead to <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content> hypertension via <jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content> activation in the kidney.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p> Renal <jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content> activity is increased in Dahl salt\u2010sensitive rats fed a high\u2010salt diet, despite the appropriate suppression of plasma aldosterone levels. In this rat strain, activation of <jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content> in the distal nephron causes salt\u2010induced hypertension. This paradoxical response of the <jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content> to salt loading can be attributed to activation of Rac1, a small <jats:styled-content style=\"fixed-case\">GTP<\/jats:styled-content>ase. In the presence of aldosterone, activated Rac1 synergistically and directly activates <jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content> in a ligand\u2010independent manner. Thus, Rac1 activation in the kidney determines the salt sensitivity of <jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content>. Together, the available evidence suggests that the aberrant Rac1\u2013<jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content> pathway plays a key role in the development of <jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content> hypertension.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p>","DOI":"10.1111\/1440-1681.12177","type":"journal-article","created":{"date-parts":[[2013,10,12]],"date-time":"2013-10-12T01:02:48Z","timestamp":1381539768000},"page":"929-936","source":"Crossref","is-referenced-by-count":22,"title":["Aberrant Rac1\u2013mineralocorticoid receptor pathways in salt\u2010sensitive hypertension"],"prefix":"10.1111","volume":"40","author":[{"given":"Wakako","family":"Kawarazaki","sequence":"first","affiliation":[{"name":"Division of Clinical Epigenetics Research Center for Advanced Science and Technology=1 The University of Tokyo=1 Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiro","family":"Fujita","sequence":"additional","affiliation":[{"name":"Division of Clinical Epigenetics Research Center for Advanced Science and Technology=1 The University of Tokyo=1 Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,11,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.5323.75"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(80)90002-9"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0828-282X(07)70802-4"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfs354"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/65.2.612S"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198908313210905"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60144-6"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-1088"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000154361.47683.d3"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000253258.36141.c7"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1879"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43124"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.19.1_Suppl.I2"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.40.4.94"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605545103"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.03.001"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-005-2344-2"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.136242"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-032149"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2891"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-118-2-819"},{"key":"e_1_2_9_23_1","first-page":"E649","article-title":"ICV infusion of corticosterone antagonizes ICV\u2010aldosterone hypertension","volume":"258","author":"G\u00f3mez S\u00e1nchez EP","year":"1990","journal-title":"Am. 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