TY - JOUR
T1 - Abnormal neonatal sodium handling in skin precedes hypertension in the SAME rat
AU - Mullins, Linda
AU - Ivy, Jessica
AU - Ward, Mairi
AU - Tenstad, Olav
AU - Wiig, Helge
AU - Kitada, Kento
AU - Manning, Jon
AU - Rakova, Natalia
AU - Muller, Dominik
AU - Mullins, John
PY - 2021/5/24
Y1 - 2021/5/24
N2 - 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.
AB - 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.
KW - Hsd11b2
KW - knockout
KW - hypertension
KW - newborn
KW - neonatal
KW - rat
KW - salt-sensitive
KW - Skin
U2 - 10.1007/s00424-021-02582-7
DO - 10.1007/s00424-021-02582-7
M3 - Article
SP - 897
JO - Pflügers Archiv European Journal of Physiology
JF - Pflügers Archiv European Journal of Physiology
SN - 0031-6768
M1 - 473
ER -