Blunted sodium excretion in response to a saline load in 5 year old female sheep following fetal uninephrectomy

Lankadeva, Yugeesh R., Singh, Reetu R., Hilliard, Lucinda M., Moritz, Karen M. and Denton, Kate M. (2012) Blunted sodium excretion in response to a saline load in 5 year old female sheep following fetal uninephrectomy. Plos One, 7 10: 47528-1-47528-10. doi:10.1371/journal.pone.0047528

Author Lankadeva, Yugeesh R.
Singh, Reetu R.
Hilliard, Lucinda M.
Moritz, Karen M.
Denton, Kate M.
Title Blunted sodium excretion in response to a saline load in 5 year old female sheep following fetal uninephrectomy
Journal name Plos One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2012-10
Sub-type Article (original research)
DOI 10.1371/journal.pone.0047528
Open Access Status DOI
Volume 7
Issue 10
Start page 47528-1
End page 47528-10
Total pages 10
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2013
Language eng
Formatted abstract
Previously, we have shown that fetal uninephrectomy (uni-x) causes hypertension in female sheep by 2 years of age. Whilst the hypertension was not exacerbated by 5 years of age, these uni-x sheep had greater reductions in renal blood flow (RBF). To further explore these early indications of a decline in renal function, we investigated the renal response to a saline load (25 ml/kg/40 min) in 5-year old female uni-x and sham sheep. Basal mean arterial pressure was ~15 mmHg greater (P Group<0.001), and sodium excretion (~50%), glomerular filtration rate (~30%, GFR) and RBF (~40%) were all significantly lower (P Group<0.01) in uni-x compared to sham animals. In response to saline loading, sodium excretion increased significantly in both groups (P Time<0.001), however this response was blunted in uni-x sheep (P GroupxTime<0.01). This was accompanied with an attenuated increase in GFR and fractional sodium excretion (both P GroupxTime<0.05), and reduced activation of the renin-angiotensin system (both P<0.05), as compared to the sham group. The reduction in sodium excretion was associated with up-regulations in the renal gene expression of NHE3 and Na +/K + ATPase α and β subunits in the kidney cortex of the uni-x compared to the sham animals (P<0.05). Notably, neither group completely excreted the saline load within the recovery period, but the uni-x retained a higher percentage of the total volume (uni-x: 48±7%; sham: 22±9%, P<0.05). In conclusion, a reduced ability to efficiently regulate extracellular fluid homeostasis is evident in female sheep at 5 years of age, which was exacerbated in animals born with a congenital nephron deficit. Whilst there was no overt exacerbation of hypertension and renal insufficiency with age in the uni-x sheep, these animals may be more vulnerable to secondary renal insults.
Keyword Reduced nephron endowment
Renal functional reserve
Pressure natriuresis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article numbere47528

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Biomedical Sciences Publications
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