{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T08:53:03Z","timestamp":1790153583011,"version":"4.0.1"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,7,3]]},"abstract":"\n Background<\/jats:title>\n \n Mineralocorticoid receptor (\n MR<\/jats:styled-content>\n ) has pathological roles in various cell types, including renal tubule cells, myocytes, and smooth muscle cells; however, the role of\n MR<\/jats:styled-content>\n in intestinal epithelial cells (\n IECs<\/jats:styled-content>\n ) has not been sufficiently evaluated. The intestine is the sensing organ of ingested sodium; accordingly, intestinal\n MR<\/jats:styled-content>\n is expected to have essential roles in blood pressure (BP) regulation.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n We generated\n IEC<\/jats:styled-content>\n \u2010specific\n MR<\/jats:styled-content>\n knockout (\n IEC<\/jats:styled-content>\n \u2010\n MR<\/jats:styled-content>\n \u2010\n KO<\/jats:styled-content>\n ) mice. With a standard diet, fecal sodium excretion was 1.5\u2010fold higher in\n IEC<\/jats:styled-content>\n \u2010\n MR<\/jats:styled-content>\n \u2010\n KO<\/jats:styled-content>\n mice, with markedly decreased colonic expression of \u03b2\u2010 and \u03b3\u2010epithelial sodium channel, than in control mice. Urinary sodium excretion in\n IEC<\/jats:styled-content>\n \u2010\n MR<\/jats:styled-content>\n \u2010\n KO<\/jats:styled-content>\n mice decreased by 30%, maintaining sodium balance; however, a low\u2010salt diet caused significant reductions in body weight and BP in\n IEC<\/jats:styled-content>\n \u2010\n MR<\/jats:styled-content>\n \u2010\n KO<\/jats:styled-content>\n mice, and plasma aldosterone exhibited a compensatory increase. With a high\u2010salt diet, intestinal sodium absorption markedly increased to similar levels in both genotypes, without an elevation in BP. Deoxycorticosterone\/salt treatment elevated BP and increased intestinal sodium absorption in both genotypes. Notably, the increase in BP was significantly smaller in\n IEC<\/jats:styled-content>\n \u2010\n MR<\/jats:styled-content>\n \u2010\n KO<\/jats:styled-content>\n mice than in control mice. The addition of the\n MR<\/jats:styled-content>\n antagonist spironolactone to deoxycorticosterone\/salt treatment eliminated the differences in BP and intestinal sodium absorption between genotypes.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Intestinal\n MR<\/jats:styled-content>\n regulates intestinal sodium absorption in the colon and contributes to BP regulation. These regulatory effects are associated with variation in epithelial sodium channel expression. These findings suggest that intestinal\n MR<\/jats:styled-content>\n is a new target for studying the molecular mechanism of hypertension and cardiovascular diseases.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.117.008259","type":"journal-article","created":{"date-parts":[[2018,6,21]],"date-time":"2018-06-21T09:15:34Z","timestamp":1529572534000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":43,"title":["Intestinal Mineralocorticoid Receptor Contributes to Epithelial Sodium Channel\u2013Mediated Intestinal Sodium Absorption and Blood Pressure Regulation"],"prefix":"10.1161","volume":"7","author":[{"given":"Toshifumi","family":"Nakamura","sequence":"first","affiliation":[{"name":"Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isao","family":"Kurihara","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakiko","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Yokota","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayano","family":"Murai\u2010Takeda","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Mitsuishi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuha","family":"Morisaki","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nao","family":"Kohata","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Oshima","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Minami","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Metabolism, Rheumatology and Nephrology Faculty of Medicine Oita University Oita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Itoh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","unstructured":"Mendis S. 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