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Redox Signaling Is an Early Event in the Pathogenesis of Renovascular Hypertension
Activation of the renin-angiotensin-aldosterone system plays a critical role in the development of chronic renal damage in patients with renovascular hypertension. Although angiotensin II (Ang II) promotes oxidative stress, inflammation, and fibrosis, it is not known how these pathways intersect to...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794800/ https://www.ncbi.nlm.nih.gov/pubmed/24025423 http://dx.doi.org/10.3390/ijms140918640 |
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author | Hartono, Stella P. Knudsen, Bruce E. Zubair, Adeel S. Nath, Karl A. Textor, Stephen J. Lerman, Lilach O. Grande, Joseph P. |
author_facet | Hartono, Stella P. Knudsen, Bruce E. Zubair, Adeel S. Nath, Karl A. Textor, Stephen J. Lerman, Lilach O. Grande, Joseph P. |
author_sort | Hartono, Stella P. |
collection | PubMed |
description | Activation of the renin-angiotensin-aldosterone system plays a critical role in the development of chronic renal damage in patients with renovascular hypertension. Although angiotensin II (Ang II) promotes oxidative stress, inflammation, and fibrosis, it is not known how these pathways intersect to produce chronic renal damage. We tested the hypothesis that renal parenchymal cells are subjected to oxidant stress early in the development of RVH and produce signals that promote influx of inflammatory cells, which may then propagate chronic renal injury. We established a reproducible murine model of RVH by placing a tetrafluoroethhylene cuff on the right renal artery. Three days after cuff placement, renal tissue demonstrates no histologic abnormalities despite up regulation of both pro- and anti-oxidant genes. Mild renal atrophy was observed after seven days and was associated with induction of Tnfα and influx of CD3+ T cells and F4/80+ macrophages. By 28 days, kidneys developed severe renal atrophy with interstitial inflammation and fibrosis, despite normalization of plasma renin activity. Based on these considerations, we propose that renal parenchymal cells initiate a progressive cascade of events leading to oxidative stress, interstitial inflammation, renal fibrosis, and atrophy. |
format | Online Article Text |
id | pubmed-3794800 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-37948002013-10-21 Redox Signaling Is an Early Event in the Pathogenesis of Renovascular Hypertension Hartono, Stella P. Knudsen, Bruce E. Zubair, Adeel S. Nath, Karl A. Textor, Stephen J. Lerman, Lilach O. Grande, Joseph P. Int J Mol Sci Article Activation of the renin-angiotensin-aldosterone system plays a critical role in the development of chronic renal damage in patients with renovascular hypertension. Although angiotensin II (Ang II) promotes oxidative stress, inflammation, and fibrosis, it is not known how these pathways intersect to produce chronic renal damage. We tested the hypothesis that renal parenchymal cells are subjected to oxidant stress early in the development of RVH and produce signals that promote influx of inflammatory cells, which may then propagate chronic renal injury. We established a reproducible murine model of RVH by placing a tetrafluoroethhylene cuff on the right renal artery. Three days after cuff placement, renal tissue demonstrates no histologic abnormalities despite up regulation of both pro- and anti-oxidant genes. Mild renal atrophy was observed after seven days and was associated with induction of Tnfα and influx of CD3+ T cells and F4/80+ macrophages. By 28 days, kidneys developed severe renal atrophy with interstitial inflammation and fibrosis, despite normalization of plasma renin activity. Based on these considerations, we propose that renal parenchymal cells initiate a progressive cascade of events leading to oxidative stress, interstitial inflammation, renal fibrosis, and atrophy. MDPI 2013-09-10 /pmc/articles/PMC3794800/ /pubmed/24025423 http://dx.doi.org/10.3390/ijms140918640 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland http://creativecommons.org/licenses/by/3.0 This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Hartono, Stella P. Knudsen, Bruce E. Zubair, Adeel S. Nath, Karl A. Textor, Stephen J. Lerman, Lilach O. Grande, Joseph P. Redox Signaling Is an Early Event in the Pathogenesis of Renovascular Hypertension |
title | Redox Signaling Is an Early Event in the Pathogenesis of Renovascular Hypertension |
title_full | Redox Signaling Is an Early Event in the Pathogenesis of Renovascular Hypertension |
title_fullStr | Redox Signaling Is an Early Event in the Pathogenesis of Renovascular Hypertension |
title_full_unstemmed | Redox Signaling Is an Early Event in the Pathogenesis of Renovascular Hypertension |
title_short | Redox Signaling Is an Early Event in the Pathogenesis of Renovascular Hypertension |
title_sort | redox signaling is an early event in the pathogenesis of renovascular hypertension |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794800/ https://www.ncbi.nlm.nih.gov/pubmed/24025423 http://dx.doi.org/10.3390/ijms140918640 |
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