Blunted sodium excretion in response to a saline load in 5 year old female sheep following fetal uninephrectomy.
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.
Department of Physiology, Monash University, Victoria, Australia.
Yugeesh R
YR
Lankadeva
Reetu R
RR
Singh
Lucinda M
LM
Hilliard
Karen M
KM
Moritz
Kate M
KM
Denton
D000818:Animals; D062186:Arterial Pressure; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced*; D009392:Nephrectomy / Q000009:adverse effects*; D012079:Renal Circulation / Q000187:drug effects*; D012756:Sheep; D012964:Sodium / Q000032:analysis; D012965:Sodium Chloride / Q000008:administration & dosage*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D012965:Sodium Chloride; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase