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Abnormal neonatal sodium handling in skin precedes hypertension in the SAME rat

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Item Type:Article
Title:Abnormal neonatal sodium handling in skin precedes hypertension in the SAME rat
Creators Name:Mullins, L. and Ivy, J. and Ward, M. and Tenstad, O. and Wiig, H. and Kitada, K. and Manning, J. and Rakova, N. and Muller, D. and Mullins, J.
Abstract:We discovered high Na(+) and water content in the skin of newborn Sprague-Dawley rats, which reduced ~ 2.5-fold by 7 days of age, indicating rapid changes in extracellular volume (ECV). Equivalent changes in ECV post birth were also observed in C57Bl/6 J mice, with a fourfold reduction over 7 days, 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(-/-) animals exhibiting lower skin Na(+) and water levels than controls at birth, they retained ~ 30% higher Na(+) content in their pelts at the expense of K(+) thereafter. Hsd11b2(-/-) neonates exhibited incipient hypokalaemia from 15 days of age and became increasingly polydipsic and polyuric from weaning. As with adults, they excreted a high proportion of ingested Na(+) through the kidney, (56.15 ± 8.21% versus control 34.15 ± 8.23%; n = 4; P < 0.0001), suggesting that changes in nephron electrolyte transporters identified in adults, by RNA-seq analysis, occur by 4 weeks of age. Our data reveal that Na(+) imbalance in the Hsd11b2(-/-) neonate leads to excess Na(+) storage in skin and incipient hypokalaemia, which, together with increased, glucocorticoid-induced Na(+) uptake in the kidney, then contribute to progressive, volume contracted, salt-sensitive hypertension. Skin Na(+) 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.
Keywords:Hsd11b2, Knockout, Hypertension, Newborn, Neonatal, Salt-sensitive, Skin, Animals, Mice, Rats
Source:Pflugers Archiv
Page Range:897-910
Date:June 2021
Official Publication:https://doi.org/10.1007/s00424-021-02582-7
PubMed:View item in PubMed

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