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Impaired ability to modulate glomerular filtration rate in aged female sheep following fetal uninephrectomy

Fetal uninephrectomy (uni‐x) results in hypertension at a later age in female than male sheep. We hypothesized that dysregulation of tubular sodium handling contributes to the reduced ability to regulate extracellular fluid (ECF) homeostasis in older females born with a congenital nephron deficit. F...

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Autores principales: Lankadeva, Yugeesh R., Singh, Reetu R., Hilliard, Lucinda M., Moritz, Karen M., Denton, Kate M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wiley Periodicals, Inc. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967691/
https://www.ncbi.nlm.nih.gov/pubmed/24744887
http://dx.doi.org/10.1002/phy2.208
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author Lankadeva, Yugeesh R.
Singh, Reetu R.
Hilliard, Lucinda M.
Moritz, Karen M.
Denton, Kate M.
author_facet Lankadeva, Yugeesh R.
Singh, Reetu R.
Hilliard, Lucinda M.
Moritz, Karen M.
Denton, Kate M.
author_sort Lankadeva, Yugeesh R.
collection PubMed
description Fetal uninephrectomy (uni‐x) results in hypertension at a later age in female than male sheep. We hypothesized that dysregulation of tubular sodium handling contributes to the reduced ability to regulate extracellular fluid (ECF) homeostasis in older females born with a congenital nephron deficit. Following renal excretory balance studies, the response to inhibition of the Na(+)K(+)2Cl(−) cotransporter with furosemide (0.5 mg/kg bolus + 1 mg/kg per hour, i.v) or vehicle treatment was examined in conscious 5‐year‐old female uni‐x (n = 7) and sham (n = 7) sheep. Balance studies in meal‐fed sheep demonstrated that while average 24 h sodium excretion over 6 days was not different between the groups, the daily variation in sodium excretion was significantly greater in uni‐x compared to sham sheep (31 ± 4% vs. 12 ± 2%; P < 0.001). Basal plasma renin activity (PRA) and renal cortical cyclooxygenase‐2 (COX‐2) gene expression were lower in uni‐x sheep (both, P < 0.01). The increases in glomerular filtration rate (GFR) and renal blood flow observed in sham sheep in response to furosemide were significantly attenuated in uni‐x sheep (both P(GROUP×TREAT) < 0.05). However, fractional sodium excretion increased by a greater extent in the uni‐x (4.4 ± 1.0%) as compared to the sham sheep (2.0 ± 0.4%; P(GROUP×TIME) < 0.05) in response to furosemide. In conclusion, fetal uni‐x was associated with altered renal sodium handling and hypertension in aged females. The impaired ability to modulate PRA and GFR in the adults with a congenital nephron deficit may reduce the capacity of the kidney to respond to gains or losses in ECF to maintain a stable internal environment.
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spelling pubmed-39676912014-04-07 Impaired ability to modulate glomerular filtration rate in aged female sheep following fetal uninephrectomy Lankadeva, Yugeesh R. Singh, Reetu R. Hilliard, Lucinda M. Moritz, Karen M. Denton, Kate M. Physiol Rep Original Research Fetal uninephrectomy (uni‐x) results in hypertension at a later age in female than male sheep. We hypothesized that dysregulation of tubular sodium handling contributes to the reduced ability to regulate extracellular fluid (ECF) homeostasis in older females born with a congenital nephron deficit. Following renal excretory balance studies, the response to inhibition of the Na(+)K(+)2Cl(−) cotransporter with furosemide (0.5 mg/kg bolus + 1 mg/kg per hour, i.v) or vehicle treatment was examined in conscious 5‐year‐old female uni‐x (n = 7) and sham (n = 7) sheep. Balance studies in meal‐fed sheep demonstrated that while average 24 h sodium excretion over 6 days was not different between the groups, the daily variation in sodium excretion was significantly greater in uni‐x compared to sham sheep (31 ± 4% vs. 12 ± 2%; P < 0.001). Basal plasma renin activity (PRA) and renal cortical cyclooxygenase‐2 (COX‐2) gene expression were lower in uni‐x sheep (both, P < 0.01). The increases in glomerular filtration rate (GFR) and renal blood flow observed in sham sheep in response to furosemide were significantly attenuated in uni‐x sheep (both P(GROUP×TREAT) < 0.05). However, fractional sodium excretion increased by a greater extent in the uni‐x (4.4 ± 1.0%) as compared to the sham sheep (2.0 ± 0.4%; P(GROUP×TIME) < 0.05) in response to furosemide. In conclusion, fetal uni‐x was associated with altered renal sodium handling and hypertension in aged females. The impaired ability to modulate PRA and GFR in the adults with a congenital nephron deficit may reduce the capacity of the kidney to respond to gains or losses in ECF to maintain a stable internal environment. Wiley Periodicals, Inc. 2014-01-28 /pmc/articles/PMC3967691/ /pubmed/24744887 http://dx.doi.org/10.1002/phy2.208 Text en © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Lankadeva, Yugeesh R.
Singh, Reetu R.
Hilliard, Lucinda M.
Moritz, Karen M.
Denton, Kate M.
Impaired ability to modulate glomerular filtration rate in aged female sheep following fetal uninephrectomy
title Impaired ability to modulate glomerular filtration rate in aged female sheep following fetal uninephrectomy
title_full Impaired ability to modulate glomerular filtration rate in aged female sheep following fetal uninephrectomy
title_fullStr Impaired ability to modulate glomerular filtration rate in aged female sheep following fetal uninephrectomy
title_full_unstemmed Impaired ability to modulate glomerular filtration rate in aged female sheep following fetal uninephrectomy
title_short Impaired ability to modulate glomerular filtration rate in aged female sheep following fetal uninephrectomy
title_sort impaired ability to modulate glomerular filtration rate in aged female sheep following fetal uninephrectomy
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967691/
https://www.ncbi.nlm.nih.gov/pubmed/24744887
http://dx.doi.org/10.1002/phy2.208
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