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Overexpression of HIF Prolyl-Hydoxylase-2 transgene in the renal medulla induced a salt sensitive hypertension

Renal medullary hypoxia-inducible factor (HIF)-1α and its target genes, such as haem oxygenase and nitric oxide synthase, have been indicated to play an important role in the regulation of sodium excretion and blood pressure. HIF prolyl hydroxylase domain-containing proteins (PHDs) are major enzymes...

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Autores principales: Zhu, Qing, Liu, Miao, Han, Wei-Qing, Li, Pin-Lan, Wang, Zhengchao, Li, Ningjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461349/
https://www.ncbi.nlm.nih.gov/pubmed/22686466
http://dx.doi.org/10.1111/j.1582-4934.2012.01590.x
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author Zhu, Qing
Liu, Miao
Han, Wei-Qing
Li, Pin-Lan
Wang, Zhengchao
Li, Ningjun
author_facet Zhu, Qing
Liu, Miao
Han, Wei-Qing
Li, Pin-Lan
Wang, Zhengchao
Li, Ningjun
author_sort Zhu, Qing
collection PubMed
description Renal medullary hypoxia-inducible factor (HIF)-1α and its target genes, such as haem oxygenase and nitric oxide synthase, have been indicated to play an important role in the regulation of sodium excretion and blood pressure. HIF prolyl hydroxylase domain-containing proteins (PHDs) are major enzymes to promote the degradation of HIF-1α. We recently reported that high salt intake suppressed the renal medullary PHD2 expression and thereby activated HIF-1α-mediated gene regulation in the renal medulla in response to high salt. To further define the functional role of renal medullary PHD2 in the regulation of renal adaptation to high salt intake and the longer term control of blood pressure, we transfected PHD2 expression plasmids into the renal medulla in uninephrectomized rats and determined its effects on pressure natriuresis, sodium excretion after salt overloading and the long-term control of arterial pressure after high salt challenge. It was shown that overexpression of PHD2 transgene increased PHD2 levels and decreased HIF-1α levels in the renal medulla, which blunted pressure natriuresis, attenuated sodium excretion, promoted sodium retention and produced salt sensitive hypertension after high salt challenge compared with rats treated with control plasmids. There was no blood pressure change in PHD2-treated rats that were maintained in low salt diet. These results suggested that renal medullary PHD2 is an important regulator in renal adaptation to high salt intake and a deficiency in PHD2-mediated molecular adaptation in response to high salt intake in the renal medulla may represent a pathogenic mechanism producing salt sensitive hypertension.
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spelling pubmed-34613492013-11-01 Overexpression of HIF Prolyl-Hydoxylase-2 transgene in the renal medulla induced a salt sensitive hypertension Zhu, Qing Liu, Miao Han, Wei-Qing Li, Pin-Lan Wang, Zhengchao Li, Ningjun J Cell Mol Med Original Articles Renal medullary hypoxia-inducible factor (HIF)-1α and its target genes, such as haem oxygenase and nitric oxide synthase, have been indicated to play an important role in the regulation of sodium excretion and blood pressure. HIF prolyl hydroxylase domain-containing proteins (PHDs) are major enzymes to promote the degradation of HIF-1α. We recently reported that high salt intake suppressed the renal medullary PHD2 expression and thereby activated HIF-1α-mediated gene regulation in the renal medulla in response to high salt. To further define the functional role of renal medullary PHD2 in the regulation of renal adaptation to high salt intake and the longer term control of blood pressure, we transfected PHD2 expression plasmids into the renal medulla in uninephrectomized rats and determined its effects on pressure natriuresis, sodium excretion after salt overloading and the long-term control of arterial pressure after high salt challenge. It was shown that overexpression of PHD2 transgene increased PHD2 levels and decreased HIF-1α levels in the renal medulla, which blunted pressure natriuresis, attenuated sodium excretion, promoted sodium retention and produced salt sensitive hypertension after high salt challenge compared with rats treated with control plasmids. There was no blood pressure change in PHD2-treated rats that were maintained in low salt diet. These results suggested that renal medullary PHD2 is an important regulator in renal adaptation to high salt intake and a deficiency in PHD2-mediated molecular adaptation in response to high salt intake in the renal medulla may represent a pathogenic mechanism producing salt sensitive hypertension. BlackWell Publishing Ltd 2012-11 2012-10-29 /pmc/articles/PMC3461349/ /pubmed/22686466 http://dx.doi.org/10.1111/j.1582-4934.2012.01590.x Text en © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
spellingShingle Original Articles
Zhu, Qing
Liu, Miao
Han, Wei-Qing
Li, Pin-Lan
Wang, Zhengchao
Li, Ningjun
Overexpression of HIF Prolyl-Hydoxylase-2 transgene in the renal medulla induced a salt sensitive hypertension
title Overexpression of HIF Prolyl-Hydoxylase-2 transgene in the renal medulla induced a salt sensitive hypertension
title_full Overexpression of HIF Prolyl-Hydoxylase-2 transgene in the renal medulla induced a salt sensitive hypertension
title_fullStr Overexpression of HIF Prolyl-Hydoxylase-2 transgene in the renal medulla induced a salt sensitive hypertension
title_full_unstemmed Overexpression of HIF Prolyl-Hydoxylase-2 transgene in the renal medulla induced a salt sensitive hypertension
title_short Overexpression of HIF Prolyl-Hydoxylase-2 transgene in the renal medulla induced a salt sensitive hypertension
title_sort overexpression of hif prolyl-hydoxylase-2 transgene in the renal medulla induced a salt sensitive hypertension
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461349/
https://www.ncbi.nlm.nih.gov/pubmed/22686466
http://dx.doi.org/10.1111/j.1582-4934.2012.01590.x
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