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Cardioprotective Effects of a Nonsteroidal Mineralocorticoid Receptor Blocker, Esaxerenone, in Dahl Salt-Sensitive Hypertensive Rats

We investigated the effects of esaxerenone, a novel, nonsteroidal, and selective mineralocorticoid receptor blocker, on cardiac function in Dahl salt-sensitive (DSS) rats. We provided 6-week-old DSS rats a high-salt diet (HSD, 8% NaCl). Following six weeks of HSD feeding (establishment of cardiac hy...

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Autores principales: Rahman, Asadur, Sawano, Tatsuya, Sen, Anupoma, Hossain, Akram, Jahan, Nourin, Kobara, Hideki, Masaki, Tsutomu, Kosaka, Shinji, Kitada, Kento, Nakano, Daisuke, Imamura, Takeshi, Ohsaki, Hiroyuki, Nishiyama, Akira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922950/
https://www.ncbi.nlm.nih.gov/pubmed/33669786
http://dx.doi.org/10.3390/ijms22042069
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author Rahman, Asadur
Sawano, Tatsuya
Sen, Anupoma
Hossain, Akram
Jahan, Nourin
Kobara, Hideki
Masaki, Tsutomu
Kosaka, Shinji
Kitada, Kento
Nakano, Daisuke
Imamura, Takeshi
Ohsaki, Hiroyuki
Nishiyama, Akira
author_facet Rahman, Asadur
Sawano, Tatsuya
Sen, Anupoma
Hossain, Akram
Jahan, Nourin
Kobara, Hideki
Masaki, Tsutomu
Kosaka, Shinji
Kitada, Kento
Nakano, Daisuke
Imamura, Takeshi
Ohsaki, Hiroyuki
Nishiyama, Akira
author_sort Rahman, Asadur
collection PubMed
description We investigated the effects of esaxerenone, a novel, nonsteroidal, and selective mineralocorticoid receptor blocker, on cardiac function in Dahl salt-sensitive (DSS) rats. We provided 6-week-old DSS rats a high-salt diet (HSD, 8% NaCl). Following six weeks of HSD feeding (establishment of cardiac hypertrophy), we divided the animals into the following two groups: HSD or HSD + esaxerenone (0.001%, w/w). In survival study, all HSD-fed animals died by 24 weeks of age, whereas the esaxerenone-treated HSD-fed animals showed significantly improved survival. We used the same protocol with a separate set of animals to evaluate the cardiac function by echocardiography after four weeks of treatment. The results showed that HSD-fed animals developed cardiac dysfunction as evidenced by reduced stroke volume, ejection fraction, and cardiac output. Importantly, esaxerenone treatment decreased the worsening of cardiac dysfunction concomitant with a significantly reduced level of systolic blood pressure. In addition, treatment with esaxerenone in HSD-fed DSS rats caused a reduced level of cardiac remodeling as well as fibrosis. Furthermore, inflammation and oxidative stress were significantly reduced. These data indicate that esaxerenone has the potential to mitigate cardiac dysfunction in salt-induced myocardial injury in rats.
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spelling pubmed-79229502021-03-03 Cardioprotective Effects of a Nonsteroidal Mineralocorticoid Receptor Blocker, Esaxerenone, in Dahl Salt-Sensitive Hypertensive Rats Rahman, Asadur Sawano, Tatsuya Sen, Anupoma Hossain, Akram Jahan, Nourin Kobara, Hideki Masaki, Tsutomu Kosaka, Shinji Kitada, Kento Nakano, Daisuke Imamura, Takeshi Ohsaki, Hiroyuki Nishiyama, Akira Int J Mol Sci Article We investigated the effects of esaxerenone, a novel, nonsteroidal, and selective mineralocorticoid receptor blocker, on cardiac function in Dahl salt-sensitive (DSS) rats. We provided 6-week-old DSS rats a high-salt diet (HSD, 8% NaCl). Following six weeks of HSD feeding (establishment of cardiac hypertrophy), we divided the animals into the following two groups: HSD or HSD + esaxerenone (0.001%, w/w). In survival study, all HSD-fed animals died by 24 weeks of age, whereas the esaxerenone-treated HSD-fed animals showed significantly improved survival. We used the same protocol with a separate set of animals to evaluate the cardiac function by echocardiography after four weeks of treatment. The results showed that HSD-fed animals developed cardiac dysfunction as evidenced by reduced stroke volume, ejection fraction, and cardiac output. Importantly, esaxerenone treatment decreased the worsening of cardiac dysfunction concomitant with a significantly reduced level of systolic blood pressure. In addition, treatment with esaxerenone in HSD-fed DSS rats caused a reduced level of cardiac remodeling as well as fibrosis. Furthermore, inflammation and oxidative stress were significantly reduced. These data indicate that esaxerenone has the potential to mitigate cardiac dysfunction in salt-induced myocardial injury in rats. MDPI 2021-02-19 /pmc/articles/PMC7922950/ /pubmed/33669786 http://dx.doi.org/10.3390/ijms22042069 Text en © 2021 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
Rahman, Asadur
Sawano, Tatsuya
Sen, Anupoma
Hossain, Akram
Jahan, Nourin
Kobara, Hideki
Masaki, Tsutomu
Kosaka, Shinji
Kitada, Kento
Nakano, Daisuke
Imamura, Takeshi
Ohsaki, Hiroyuki
Nishiyama, Akira
Cardioprotective Effects of a Nonsteroidal Mineralocorticoid Receptor Blocker, Esaxerenone, in Dahl Salt-Sensitive Hypertensive Rats
title Cardioprotective Effects of a Nonsteroidal Mineralocorticoid Receptor Blocker, Esaxerenone, in Dahl Salt-Sensitive Hypertensive Rats
title_full Cardioprotective Effects of a Nonsteroidal Mineralocorticoid Receptor Blocker, Esaxerenone, in Dahl Salt-Sensitive Hypertensive Rats
title_fullStr Cardioprotective Effects of a Nonsteroidal Mineralocorticoid Receptor Blocker, Esaxerenone, in Dahl Salt-Sensitive Hypertensive Rats
title_full_unstemmed Cardioprotective Effects of a Nonsteroidal Mineralocorticoid Receptor Blocker, Esaxerenone, in Dahl Salt-Sensitive Hypertensive Rats
title_short Cardioprotective Effects of a Nonsteroidal Mineralocorticoid Receptor Blocker, Esaxerenone, in Dahl Salt-Sensitive Hypertensive Rats
title_sort cardioprotective effects of a nonsteroidal mineralocorticoid receptor blocker, esaxerenone, in dahl salt-sensitive hypertensive rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922950/
https://www.ncbi.nlm.nih.gov/pubmed/33669786
http://dx.doi.org/10.3390/ijms22042069
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