{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:39:15Z","timestamp":1781642355536,"version":"3.54.5"},"reference-count":61,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL147818"],"award-info":[{"award-number":["R01HL147818"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Aldosterone is responsible for maintaining volume and potassium homeostasis. Although high salt consumption should suppress aldosterone production, individuals with hyperaldosteronism lose this regulation, leading to a state of high aldosterone despite dietary sodium consumption. The present study examines the effects of elevated aldosterone, with or without high salt consumption, on the expression of key Na<jats:sup>+<\/jats:sup> transporters and remodelling in the distal nephron. Epithelial sodium channel (ENaC) \u03b1\u2010subunit expression was increased with aldosterone regardless of Na<jats:sup>+<\/jats:sup> intake. However, ENaC \u03b2\u2010 and \u03b3\u2010subunits unexpectedly increased at both a transcript and protein level with aldosterone when high salt was present. Expression of total and phosphorylated Na<jats:sup>+<\/jats:sup>Cl<jats:sup>\u2212<\/jats:sup> cotransporter (NCC) significantly increased with aldosterone, in association with decreased blood [K<jats:sup>+<\/jats:sup>], but the addition of high salt markedly attenuated the aldosterone\u2010dependent NCC increase, despite equally severe hypokalaemia. We hypothesized this was a result of differences in distal convoluted tubule length when salt was given with aldosterone. Imaging and measurement of the entire pNCC\u2010positive tubule revealed that aldosterone alone caused a shortening of this segment, although the tubule had a larger cross\u2010sectional diameter. This was not true when salt was given with aldosterone because the combination was associated with a lengthening of the tubule in addition to increased diameter, suggesting that differences in the pNCC\u2010positive area are not responsible for differences in NCC expression. Together, our results suggest the actions of aldosterone, and the subsequent changes related to hypokalaemia, are altered in the presence of high dietary Na<jats:sup>+<\/jats:sup>.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15916-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Aldosterone regulates volume and potassium homeostasis through effects on transporters in the kidney; its production can be dysregulated, preventing its suppression by high dietary sodium intake.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Here, we examined how chronic high sodium consumption affects aldosterone's regulation of sodium transporters in the distal nephron.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our results suggest that high sodium consumption with aldosterone is associated with increased expression of all three epithelial sodium channel subunits, rather than just the alpha subunit.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Aldosterone and its associated decrease in blood [K<jats:sup>+<\/jats:sup>] lead to an increased expression of Na\u2010Cl cotransporter (NCC); the addition of high sodium consumption with aldosterone partially attenuates this NCC expression, despite similarly low blood [K<jats:sup>+<\/jats:sup>].<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Upstream kinase regulators and tubule remodelling do not explain these results.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp284041","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T16:25:29Z","timestamp":1706718329000},"page":"967-987","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Dietary sodium alters aldosterone's effect on renal sodium transporter expression and distal convoluted tubule remodelling"],"prefix":"10.1113","volume":"602","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4288-4452","authenticated-orcid":false,"given":"Stephanie M.","family":"Mutchler","sequence":"first","affiliation":[{"name":"Department of Medicine University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahpara","family":"Hasan","sequence":"additional","affiliation":[{"name":"Carnegie Mellon University  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn P.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine J.","family":"Baty","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cary","family":"Boyd\u2010Shiwarski","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annet","family":"Kirabo","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Department of Medicine and Department of Molecular Physiology and Biophysics Vanderbilt University  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2413-5415","authenticated-orcid":false,"given":"Thomas R.","family":"Kleyman","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Pittsburgh  Pittsburgh PA USA"},{"name":"Department of Cell Biology University of Pittsburgh  Pittsburgh PA USA"},{"name":"Department of Pharmacology and Chemical Biology University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.120.16440"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1996.271.2.C605"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.regpep.2009.10.002"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000066129.12106.E2"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2017030345"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E17-08-0529"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00527.2019"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1100522"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1817220116"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.5.2514"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2018101025"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.451"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.24.7052"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000001558"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00585.2014"},{"issue":"1","key":"e_1_2_5_17_1","first-page":"R86","article-title":"Proximal tubule response in aldosterone escape","volume":"256","author":"Gonzalez\u2010Campoy J. 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