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Equivalent changes in ECV post birth were also observed in C57Bl\/6\u00a0J mice, with a fourfold reduction over 7\u00a0days, to approximately adult levels. This established the generality of increased ECV at birth. We investigated early sodium and water handling in neonates from a second rat strain, Fischer, and an Hsd11b2-knockout rat modelling the syndrome of apparent mineralocorticoid excess (SAME). Despite Hsd11b2<jats:sup>\u2212\/\u2212<\/jats:sup> animals exhibiting lower skin Na<jats:sup>+<\/jats:sup> and water levels than controls at birth, they retained\u2009~\u200930% higher Na<jats:sup>+<\/jats:sup> content in their pelts at the expense of K<jats:sup>+<\/jats:sup> thereafter. Hsd11b2<jats:sup>\u2212\/\u2212<\/jats:sup> neonates exhibited incipient hypokalaemia from 15\u00a0days of age and became increasingly polydipsic and polyuric from weaning. As with adults, they excreted a high proportion of ingested Na<jats:sup>+<\/jats:sup> through the kidney, (56.15\u2009\u00b1\u20098.21% versus control 34.15\u2009\u00b1\u20098.23%; n\u2009=\u20094; P\u2009&lt;\u20090.0001), suggesting that changes in nephron electrolyte transporters identified in adults, by RNA-seq analysis, occur by 4\u00a0weeks of age. Our data reveal that Na<jats:sup>+<\/jats:sup> imbalance in the Hsd11b2<jats:sup>\u2212\/\u2212<\/jats:sup> neonate leads to excess Na<jats:sup>+<\/jats:sup> storage in skin and incipient hypokalaemia, which, together with increased, glucocorticoid-induced Na<jats:sup>+<\/jats:sup> uptake in the kidney, then contribute to progressive, volume contracted, salt-sensitive hypertension. Skin Na<jats:sup>+<\/jats:sup> plays an important role in the development of SAME but, equally, may play a key physiological role at birth, supporting post-natal growth, as an innate barrier to infection or as a rudimentary kidney.<\/jats:p>","DOI":"10.1007\/s00424-021-02582-7","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T04:02:41Z","timestamp":1621828961000},"page":"897-910","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Abnormal neonatal sodium handling in skin precedes hypertension in the SAME rat"],"prefix":"10.1007","volume":"473","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6743-8707","authenticated-orcid":false,"given":"Linda","family":"Mullins","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Ivy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mairi","family":"Ward","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olav","family":"Tenstad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helge","family":"Wiig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kento","family":"Kitada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jon","family":"Manning","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Rakova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominik","family":"Muller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Mullins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,5,24]]},"reference":[{"key":"2582_CR1","doi-asserted-by":"publisher","first-page":"F655","DOI":"10.1152\/ajprenal.2000.279.4.F655","volume":"279","author":"H Amlal","year":"2000","unstructured":"Amlal H, Krane CM, Chen Q, Soleimani M (2000) Early polyuria and urinary concentrating defect in potassium deprivation. 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