Abstract / Description of output
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/6J mice, with a 4-fold 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.
Original language | English |
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Article number | 473 |
Pages (from-to) | 897 |
Number of pages | 910 |
Journal | Pflügers Archiv European Journal of Physiology |
DOIs | |
Publication status | Published - 24 May 2021 |
Keywords / Materials (for Non-textual outputs)
- Hsd11b2
- knockout
- hypertension
- newborn
- neonatal
- rat
- salt-sensitive
- Skin