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 declin...

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Veröffentlicht in:PloS one 2012-10, Vol.7 (10), p.e47528
Hauptverfasser: Lankadeva, Yugeesh R, Singh, Reetu R, Hilliard, Lucinda M, Moritz, Karen M, Denton, Kate M
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Singh, Reetu R
Hilliard, Lucinda M
Moritz, Karen M
Denton, Kate M
description 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)
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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.]]></description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0047528</identifier><identifier>PMID: 23077628</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Age ; Angiotensin ; Angiotensins ; Animals ; Arterial Pressure ; Biology ; Blood flow ; Blood pressure ; Cardiovascular disease ; Congenital diseases ; Development and progression ; Endowment ; Excretion ; Female ; Females ; Fetuses ; Gene expression ; Gene Expression - drug effects ; Genetic aspects ; Glomerular filtration rate ; Glomerular Filtration Rate - drug effects ; Homeostasis ; Hypertension ; Hypertension - chemically induced ; Kidney diseases ; Males ; Medicine ; Na+/K+-exchanging ATPase ; Nephrectomy - adverse effects ; Ovis aries ; Physiology ; Psychological aspects ; Renal Circulation - drug effects ; Renal cortex ; Renal function ; Renal insufficiency ; Renin ; Risk factors ; Rodents ; Sheep ; Sodium ; Sodium - analysis ; Sodium Chloride - administration &amp; dosage ; Sodium-Potassium-Exchanging ATPase - metabolism ; Surgery ; Veterinary Science</subject><ispartof>PloS one, 2012-10, Vol.7 (10), p.e47528</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>Lankadeva et al. 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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.]]></description><subject>Age</subject><subject>Angiotensin</subject><subject>Angiotensins</subject><subject>Animals</subject><subject>Arterial Pressure</subject><subject>Biology</subject><subject>Blood flow</subject><subject>Blood pressure</subject><subject>Cardiovascular disease</subject><subject>Congenital diseases</subject><subject>Development and progression</subject><subject>Endowment</subject><subject>Excretion</subject><subject>Female</subject><subject>Females</subject><subject>Fetuses</subject><subject>Gene expression</subject><subject>Gene Expression - drug effects</subject><subject>Genetic aspects</subject><subject>Glomerular filtration rate</subject><subject>Glomerular Filtration Rate - drug effects</subject><subject>Homeostasis</subject><subject>Hypertension</subject><subject>Hypertension - chemically induced</subject><subject>Kidney diseases</subject><subject>Males</subject><subject>Medicine</subject><subject>Na+/K+-exchanging ATPase</subject><subject>Nephrectomy - adverse effects</subject><subject>Ovis aries</subject><subject>Physiology</subject><subject>Psychological aspects</subject><subject>Renal Circulation - drug effects</subject><subject>Renal cortex</subject><subject>Renal function</subject><subject>Renal insufficiency</subject><subject>Renin</subject><subject>Risk factors</subject><subject>Rodents</subject><subject>Sheep</subject><subject>Sodium</subject><subject>Sodium - analysis</subject><subject>Sodium Chloride - administration &amp; 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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.]]></abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23077628</pmid><doi>10.1371/journal.pone.0047528</doi><tpages>e47528</tpages><oa>free_for_read</oa></addata></record>
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subjects Age
Angiotensin
Angiotensins
Animals
Arterial Pressure
Biology
Blood flow
Blood pressure
Cardiovascular disease
Congenital diseases
Development and progression
Endowment
Excretion
Female
Females
Fetuses
Gene expression
Gene Expression - drug effects
Genetic aspects
Glomerular filtration rate
Glomerular Filtration Rate - drug effects
Homeostasis
Hypertension
Hypertension - chemically induced
Kidney diseases
Males
Medicine
Na+/K+-exchanging ATPase
Nephrectomy - adverse effects
Ovis aries
Physiology
Psychological aspects
Renal Circulation - drug effects
Renal cortex
Renal function
Renal insufficiency
Renin
Risk factors
Rodents
Sheep
Sodium
Sodium - analysis
Sodium Chloride - administration & dosage
Sodium-Potassium-Exchanging ATPase - metabolism
Surgery
Veterinary Science
title Blunted sodium excretion in response to a saline load in 5 year old female sheep following fetal uninephrectomy
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