Cargando…
Eplerenone-Resistant Salt-Sensitive Hypertension in Nedd4-2 C2 KO Mice
The epithelial sodium channel (ENaC) plays critical roles in maintaining fluid and electrolyte homeostasis and is located in the aldosterone-sensitive distal nephron (ASDN). We previously found that Nedd4-2 C2 knockout (KO) mice showed salt-sensitive hypertension with paradoxically enhanced ENaC gen...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486073/ https://www.ncbi.nlm.nih.gov/pubmed/28604611 http://dx.doi.org/10.3390/ijms18061250 |
_version_ | 1783246194860883968 |
---|---|
author | Kino, Tabito Ishigami, Tomoaki Murata, Tsumugi Doi, Hiroshi Nakashima-Sasaki, Rie Chen, Lin Sugiyama, Michiko Azushima, Kengo Wakui, Hiromichi Minegishi, Shintaro Tamura, Kouichi |
author_facet | Kino, Tabito Ishigami, Tomoaki Murata, Tsumugi Doi, Hiroshi Nakashima-Sasaki, Rie Chen, Lin Sugiyama, Michiko Azushima, Kengo Wakui, Hiromichi Minegishi, Shintaro Tamura, Kouichi |
author_sort | Kino, Tabito |
collection | PubMed |
description | The epithelial sodium channel (ENaC) plays critical roles in maintaining fluid and electrolyte homeostasis and is located in the aldosterone-sensitive distal nephron (ASDN). We previously found that Nedd4-2 C2 knockout (KO) mice showed salt-sensitive hypertension with paradoxically enhanced ENaC gene expression in ASDN under high oral salt intake. Eplerenone (EPL), a selective aldosterone blocker, is a promising therapeutic option for resistant or/and salt-sensitive hypertension. We examined the effect of EPL on Nedd4-2 C2 KO mice with respect to blood pressure, metabolic parameters, and molecular level changes in ASDN under high oral salt intake. We found that EPL failed to reduce blood pressure in KO mice with high oral salt intake and upregulated ENaC expression in ASDN. Thus, salt-sensitive hypertension in Nedd4-2 C2 KO was EPL-resistant. Gene expression analyses of laser-captured specimens in ASDN suggested the presence of non-aldosterone-dependent activation of ENaC transcription in ASDN of Nedd4-2 C2 KO mice, which was abolished by amiloride treatment. Our results from Nedd4-2 C2 KO mice suggest that enhanced ENaC gene expression is critically involved in salt-sensitive hypertension under certain conditions of specific enzyme isoforms for their ubiquitination. |
format | Online Article Text |
id | pubmed-5486073 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-54860732017-06-29 Eplerenone-Resistant Salt-Sensitive Hypertension in Nedd4-2 C2 KO Mice Kino, Tabito Ishigami, Tomoaki Murata, Tsumugi Doi, Hiroshi Nakashima-Sasaki, Rie Chen, Lin Sugiyama, Michiko Azushima, Kengo Wakui, Hiromichi Minegishi, Shintaro Tamura, Kouichi Int J Mol Sci Article The epithelial sodium channel (ENaC) plays critical roles in maintaining fluid and electrolyte homeostasis and is located in the aldosterone-sensitive distal nephron (ASDN). We previously found that Nedd4-2 C2 knockout (KO) mice showed salt-sensitive hypertension with paradoxically enhanced ENaC gene expression in ASDN under high oral salt intake. Eplerenone (EPL), a selective aldosterone blocker, is a promising therapeutic option for resistant or/and salt-sensitive hypertension. We examined the effect of EPL on Nedd4-2 C2 KO mice with respect to blood pressure, metabolic parameters, and molecular level changes in ASDN under high oral salt intake. We found that EPL failed to reduce blood pressure in KO mice with high oral salt intake and upregulated ENaC expression in ASDN. Thus, salt-sensitive hypertension in Nedd4-2 C2 KO was EPL-resistant. Gene expression analyses of laser-captured specimens in ASDN suggested the presence of non-aldosterone-dependent activation of ENaC transcription in ASDN of Nedd4-2 C2 KO mice, which was abolished by amiloride treatment. Our results from Nedd4-2 C2 KO mice suggest that enhanced ENaC gene expression is critically involved in salt-sensitive hypertension under certain conditions of specific enzyme isoforms for their ubiquitination. MDPI 2017-06-11 /pmc/articles/PMC5486073/ /pubmed/28604611 http://dx.doi.org/10.3390/ijms18061250 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kino, Tabito Ishigami, Tomoaki Murata, Tsumugi Doi, Hiroshi Nakashima-Sasaki, Rie Chen, Lin Sugiyama, Michiko Azushima, Kengo Wakui, Hiromichi Minegishi, Shintaro Tamura, Kouichi Eplerenone-Resistant Salt-Sensitive Hypertension in Nedd4-2 C2 KO Mice |
title | Eplerenone-Resistant Salt-Sensitive Hypertension in Nedd4-2 C2 KO Mice |
title_full | Eplerenone-Resistant Salt-Sensitive Hypertension in Nedd4-2 C2 KO Mice |
title_fullStr | Eplerenone-Resistant Salt-Sensitive Hypertension in Nedd4-2 C2 KO Mice |
title_full_unstemmed | Eplerenone-Resistant Salt-Sensitive Hypertension in Nedd4-2 C2 KO Mice |
title_short | Eplerenone-Resistant Salt-Sensitive Hypertension in Nedd4-2 C2 KO Mice |
title_sort | eplerenone-resistant salt-sensitive hypertension in nedd4-2 c2 ko mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486073/ https://www.ncbi.nlm.nih.gov/pubmed/28604611 http://dx.doi.org/10.3390/ijms18061250 |
work_keys_str_mv | AT kinotabito eplerenoneresistantsaltsensitivehypertensioninnedd42c2komice AT ishigamitomoaki eplerenoneresistantsaltsensitivehypertensioninnedd42c2komice AT muratatsumugi eplerenoneresistantsaltsensitivehypertensioninnedd42c2komice AT doihiroshi eplerenoneresistantsaltsensitivehypertensioninnedd42c2komice AT nakashimasasakirie eplerenoneresistantsaltsensitivehypertensioninnedd42c2komice AT chenlin eplerenoneresistantsaltsensitivehypertensioninnedd42c2komice AT sugiyamamichiko eplerenoneresistantsaltsensitivehypertensioninnedd42c2komice AT azushimakengo eplerenoneresistantsaltsensitivehypertensioninnedd42c2komice AT wakuihiromichi eplerenoneresistantsaltsensitivehypertensioninnedd42c2komice AT minegishishintaro eplerenoneresistantsaltsensitivehypertensioninnedd42c2komice AT tamurakouichi eplerenoneresistantsaltsensitivehypertensioninnedd42c2komice |