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Improvement in Renal Hemodynamics following Combined Angiotensin II Infusion and AT1R Blockade in Aged Female Sheep following Fetal Unilateral Nephrectomy
Renin-angiotensin system (RAS) is a powerful modulator of renal hemodynamic and fluid homeostasis. Up-regulation in components of intra-renal RAS occurs with ageing. Recently we reported that 2 year old uninephrectomised (uni-x) female sheep have low renin hypertension and reduced renal function. By...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3698080/ https://www.ncbi.nlm.nih.gov/pubmed/23840884 http://dx.doi.org/10.1371/journal.pone.0068036 |
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author | Singh, Reetu R. Lankadeva, Yugeesh R. Denton, Kate M. Moritz, Karen M. |
author_facet | Singh, Reetu R. Lankadeva, Yugeesh R. Denton, Kate M. Moritz, Karen M. |
author_sort | Singh, Reetu R. |
collection | PubMed |
description | Renin-angiotensin system (RAS) is a powerful modulator of renal hemodynamic and fluid homeostasis. Up-regulation in components of intra-renal RAS occurs with ageing. Recently we reported that 2 year old uninephrectomised (uni-x) female sheep have low renin hypertension and reduced renal function. By 5 years of age, these uni-x sheep had augmented decrease in renal blood flow (RBF) compared to sham. We hypothesised that this decrease in RBF in 5 year old uni-x sheep was due to an up-regulation in components of the intra-renal RAS. In this study, renal responses to angiotensin II (AngII) infusion and AngII type 1 receptor (AT1R) blockade were examined in the same 5 year old sheep. We also administered AngII in the presence of losartan to increase AngII bioavailability to the AT2R in order to understand AT2R contribution to renal function in this model. Uni-x animals had significantly lower renal cortical content of renin, AngII (∼40%) and Ang 1–7 (∼60%) and reduced cortical expression of AT1R gene than sham animals. In response to both AngII infusion and AT1R blockade via losartan, renal hemodynamic responses and tubular sodium excretion were significantly attenuated in uni-x animals compared to sham. However, AngII infusion in the presence of losartan caused ∼33% increase in RBF in uni-x sheep compared to ∼14% in sham (P<0.05). This was associated with a significant decrease in renal vascular resistance in the uni-x animals (22% vs 15%, P<0.05) without any changes in systemic blood pressure. The present study shows that majority of the intra-renal RAS components are suppressed in this model of low renin hypertension. However, increasing the availability of AngII to AT2R by AT1R blockade improved renal blood flow in uni-x sheep. This suggests that manipulation of the AT2R maybe a potential therapeutic target for treatment of renal dysfunction associated with a congenital nephron deficit. |
format | Online Article Text |
id | pubmed-3698080 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-36980802013-07-09 Improvement in Renal Hemodynamics following Combined Angiotensin II Infusion and AT1R Blockade in Aged Female Sheep following Fetal Unilateral Nephrectomy Singh, Reetu R. Lankadeva, Yugeesh R. Denton, Kate M. Moritz, Karen M. PLoS One Research Article Renin-angiotensin system (RAS) is a powerful modulator of renal hemodynamic and fluid homeostasis. Up-regulation in components of intra-renal RAS occurs with ageing. Recently we reported that 2 year old uninephrectomised (uni-x) female sheep have low renin hypertension and reduced renal function. By 5 years of age, these uni-x sheep had augmented decrease in renal blood flow (RBF) compared to sham. We hypothesised that this decrease in RBF in 5 year old uni-x sheep was due to an up-regulation in components of the intra-renal RAS. In this study, renal responses to angiotensin II (AngII) infusion and AngII type 1 receptor (AT1R) blockade were examined in the same 5 year old sheep. We also administered AngII in the presence of losartan to increase AngII bioavailability to the AT2R in order to understand AT2R contribution to renal function in this model. Uni-x animals had significantly lower renal cortical content of renin, AngII (∼40%) and Ang 1–7 (∼60%) and reduced cortical expression of AT1R gene than sham animals. In response to both AngII infusion and AT1R blockade via losartan, renal hemodynamic responses and tubular sodium excretion were significantly attenuated in uni-x animals compared to sham. However, AngII infusion in the presence of losartan caused ∼33% increase in RBF in uni-x sheep compared to ∼14% in sham (P<0.05). This was associated with a significant decrease in renal vascular resistance in the uni-x animals (22% vs 15%, P<0.05) without any changes in systemic blood pressure. The present study shows that majority of the intra-renal RAS components are suppressed in this model of low renin hypertension. However, increasing the availability of AngII to AT2R by AT1R blockade improved renal blood flow in uni-x sheep. This suggests that manipulation of the AT2R maybe a potential therapeutic target for treatment of renal dysfunction associated with a congenital nephron deficit. Public Library of Science 2013-07-01 /pmc/articles/PMC3698080/ /pubmed/23840884 http://dx.doi.org/10.1371/journal.pone.0068036 Text en © 2013 Singh et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Singh, Reetu R. Lankadeva, Yugeesh R. Denton, Kate M. Moritz, Karen M. Improvement in Renal Hemodynamics following Combined Angiotensin II Infusion and AT1R Blockade in Aged Female Sheep following Fetal Unilateral Nephrectomy |
title | Improvement in Renal Hemodynamics following Combined Angiotensin II Infusion and AT1R Blockade in Aged Female Sheep following Fetal Unilateral Nephrectomy |
title_full | Improvement in Renal Hemodynamics following Combined Angiotensin II Infusion and AT1R Blockade in Aged Female Sheep following Fetal Unilateral Nephrectomy |
title_fullStr | Improvement in Renal Hemodynamics following Combined Angiotensin II Infusion and AT1R Blockade in Aged Female Sheep following Fetal Unilateral Nephrectomy |
title_full_unstemmed | Improvement in Renal Hemodynamics following Combined Angiotensin II Infusion and AT1R Blockade in Aged Female Sheep following Fetal Unilateral Nephrectomy |
title_short | Improvement in Renal Hemodynamics following Combined Angiotensin II Infusion and AT1R Blockade in Aged Female Sheep following Fetal Unilateral Nephrectomy |
title_sort | improvement in renal hemodynamics following combined angiotensin ii infusion and at1r blockade in aged female sheep following fetal unilateral nephrectomy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3698080/ https://www.ncbi.nlm.nih.gov/pubmed/23840884 http://dx.doi.org/10.1371/journal.pone.0068036 |
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