Increased cardiovascular and renal risk is associated with low nephron endowment in aged females: an ovine model of fetal unilateral nephrectomy.

Previously we have shown that ovariectomised (OVX) female sheep have reduced renal function and elevated blood pressure from 6 months of age following fetal uninephrectomy (uni-x) at 100 days of gestation (term = 150 days). In the current study we examined if in intact female sheep the onset of decl...

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Autores principales:	Reetu R Singh, Andrew J Jefferies, Yugeesh R Lankadeva, Paul Lombardo, Michal Schneider-Kolsky, Lucinda Hilliard, Kate M Denton, Karen M Moritz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/32692361cc614cc89402215525e17baa
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spelling	oai:doaj.org-article:32692361cc614cc89402215525e17baa2021-11-18T07:09:47ZIncreased cardiovascular and renal risk is associated with low nephron endowment in aged females: an ovine model of fetal unilateral nephrectomy.1932-620310.1371/journal.pone.0042400https://doaj.org/article/32692361cc614cc89402215525e17baa2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22879965/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Previously we have shown that ovariectomised (OVX) female sheep have reduced renal function and elevated blood pressure from 6 months of age following fetal uninephrectomy (uni-x) at 100 days of gestation (term = 150 days). In the current study we examined if in intact female sheep the onset of decline in renal function and elevation in blood pressure was prevented. Studies were performed at 1 year, 2 and 5 years of age. Following fetal uni-x at 100 days, intact female sheep had ~30% reduction in glomerular filtration rate (GFR) at 1 year, which did not exacerbate with age (P(treatment) = 0.0001, P(age) = 0.7). In contrast renal blood flow was similar between the treatment groups at 1 year of age but had declined in the uni-x animals at 5 years of age (P(treatment × age) = 0.046). Interestingly, intact uni-x sheep did not develop elevations in arterial pressure until 2 years of age. Furthermore, uni-x animals had a similar capacity to respond to a cardiac challenge at 1 year and 2 years of age, however, cardiac functional reserve was significantly reduced compared to sham group at 5 years of age. Uni-x animals exhibited an increase in left ventricular dimensions at 5 years of age compared to the sham animals and compared to 2 years of age (P(treatment)<0.001, P(treatment × age)<0.001). In conclusion, the onset of renal dysfunction preceded the onset of hypertension in intact female uni-x sheep. Furthermore, this study showed that the intact females are protected from the impact of a reduced nephron endowment on cardiovascular health early in life as opposed to our findings in young male sheep and OVX uni-x female sheep. However, with ageing this protection is lost as evidenced by presence of left ventricular hypertrophy and impaired cardiac function in 5 year old uni-x female sheep.Reetu R SinghAndrew J JefferiesYugeesh R LankadevaPaul LombardoMichal Schneider-KolskyLucinda HilliardKate M DentonKaren M MoritzPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e42400 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Reetu R Singh Andrew J Jefferies Yugeesh R Lankadeva Paul Lombardo Michal Schneider-Kolsky Lucinda Hilliard Kate M Denton Karen M Moritz Increased cardiovascular and renal risk is associated with low nephron endowment in aged females: an ovine model of fetal unilateral nephrectomy.
description	Previously we have shown that ovariectomised (OVX) female sheep have reduced renal function and elevated blood pressure from 6 months of age following fetal uninephrectomy (uni-x) at 100 days of gestation (term = 150 days). In the current study we examined if in intact female sheep the onset of decline in renal function and elevation in blood pressure was prevented. Studies were performed at 1 year, 2 and 5 years of age. Following fetal uni-x at 100 days, intact female sheep had ~30% reduction in glomerular filtration rate (GFR) at 1 year, which did not exacerbate with age (P(treatment) = 0.0001, P(age) = 0.7). In contrast renal blood flow was similar between the treatment groups at 1 year of age but had declined in the uni-x animals at 5 years of age (P(treatment × age) = 0.046). Interestingly, intact uni-x sheep did not develop elevations in arterial pressure until 2 years of age. Furthermore, uni-x animals had a similar capacity to respond to a cardiac challenge at 1 year and 2 years of age, however, cardiac functional reserve was significantly reduced compared to sham group at 5 years of age. Uni-x animals exhibited an increase in left ventricular dimensions at 5 years of age compared to the sham animals and compared to 2 years of age (P(treatment)<0.001, P(treatment × age)<0.001). In conclusion, the onset of renal dysfunction preceded the onset of hypertension in intact female uni-x sheep. Furthermore, this study showed that the intact females are protected from the impact of a reduced nephron endowment on cardiovascular health early in life as opposed to our findings in young male sheep and OVX uni-x female sheep. However, with ageing this protection is lost as evidenced by presence of left ventricular hypertrophy and impaired cardiac function in 5 year old uni-x female sheep.
format	article
author	Reetu R Singh Andrew J Jefferies Yugeesh R Lankadeva Paul Lombardo Michal Schneider-Kolsky Lucinda Hilliard Kate M Denton Karen M Moritz
author_facet	Reetu R Singh Andrew J Jefferies Yugeesh R Lankadeva Paul Lombardo Michal Schneider-Kolsky Lucinda Hilliard Kate M Denton Karen M Moritz
author_sort	Reetu R Singh
title	Increased cardiovascular and renal risk is associated with low nephron endowment in aged females: an ovine model of fetal unilateral nephrectomy.
title_short	Increased cardiovascular and renal risk is associated with low nephron endowment in aged females: an ovine model of fetal unilateral nephrectomy.
title_full	Increased cardiovascular and renal risk is associated with low nephron endowment in aged females: an ovine model of fetal unilateral nephrectomy.
title_fullStr	Increased cardiovascular and renal risk is associated with low nephron endowment in aged females: an ovine model of fetal unilateral nephrectomy.
title_full_unstemmed	Increased cardiovascular and renal risk is associated with low nephron endowment in aged females: an ovine model of fetal unilateral nephrectomy.
title_sort	increased cardiovascular and renal risk is associated with low nephron endowment in aged females: an ovine model of fetal unilateral nephrectomy.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/32692361cc614cc89402215525e17baa
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Increased cardiovascular and renal risk is associated with low nephron endowment in aged females: an ovine model of fetal unilateral nephrectomy.

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