Comparison of the antiremodeling effects of losartan and mirabegron in a rat model of uremic cardiomyopathy

Abstract Uremic cardiomyopathy is characterized by diastolic dysfunction (DD), left ventricular hypertrophy (LVH), and fibrosis. Angiotensin-II plays a major role in the development of uremic cardiomyopathy via nitro-oxidative and inflammatory mechanisms. In heart failure, the beta-3 adrenergic rece...

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Autores principales:	Zsuzsanna Z. A. Kovács, Gergő Szűcs, Marah Freiwan, Mónika G. Kovács, Fanni M. Márványkövi, Hoa Dinh, Andrea Siska, Katalin Farkas, Ferenc Kovács, András Kriston, Péter Horváth, Bence Kővári, Bálint Gábor Cserni, Gábor Cserni, Imre Földesi, Tamás Csont, Márta Sárközy
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3ad90176f4df4c6c9713c509cda2b33c
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spelling	oai:doaj.org-article:3ad90176f4df4c6c9713c509cda2b33c2021-12-02T15:29:02ZComparison of the antiremodeling effects of losartan and mirabegron in a rat model of uremic cardiomyopathy10.1038/s41598-021-96815-52045-2322https://doaj.org/article/3ad90176f4df4c6c9713c509cda2b33c2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96815-5https://doaj.org/toc/2045-2322Abstract Uremic cardiomyopathy is characterized by diastolic dysfunction (DD), left ventricular hypertrophy (LVH), and fibrosis. Angiotensin-II plays a major role in the development of uremic cardiomyopathy via nitro-oxidative and inflammatory mechanisms. In heart failure, the beta-3 adrenergic receptor (β3-AR) is up-regulated and coupled to endothelial nitric oxide synthase (eNOS)-mediated pathways, exerting antiremodeling effects. We aimed to compare the antiremodeling effects of the angiotensin-II receptor blocker losartan and the β3-AR agonist mirabegron in uremic cardiomyopathy. Chronic kidney disease (CKD) was induced by 5/6th nephrectomy in male Wistar rats. Five weeks later, rats were randomized into four groups: (1) sham-operated, (2) CKD, (3) losartan-treated (10 mg/kg/day) CKD, and (4) mirabegron-treated (10 mg/kg/day) CKD groups. At week 13, echocardiographic, histologic, laboratory, qRT-PCR, and Western blot measurements proved the development of uremic cardiomyopathy with DD, LVH, fibrosis, inflammation, and reduced eNOS levels, which were significantly ameliorated by losartan. However, mirabegron showed a tendency to decrease DD and fibrosis; but eNOS expression remained reduced. In uremic cardiomyopathy, β3-AR, sarcoplasmic reticulum ATPase (SERCA), and phospholamban levels did not change irrespective of treatments. Mirabegron reduced the angiotensin-II receptor 1 expression in uremic cardiomyopathy that might explain its mild antiremodeling effects despite the unchanged expression of the β3-AR.Zsuzsanna Z. A. KovácsGergő SzűcsMarah FreiwanMónika G. KovácsFanni M. MárványköviHoa DinhAndrea SiskaKatalin FarkasFerenc KovácsAndrás KristonPéter HorváthBence KőváriBálint Gábor CserniGábor CserniImre FöldesiTamás CsontMárta SárközyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zsuzsanna Z. A. Kovács Gergő Szűcs Marah Freiwan Mónika G. Kovács Fanni M. Márványkövi Hoa Dinh Andrea Siska Katalin Farkas Ferenc Kovács András Kriston Péter Horváth Bence Kővári Bálint Gábor Cserni Gábor Cserni Imre Földesi Tamás Csont Márta Sárközy Comparison of the antiremodeling effects of losartan and mirabegron in a rat model of uremic cardiomyopathy
description	Abstract Uremic cardiomyopathy is characterized by diastolic dysfunction (DD), left ventricular hypertrophy (LVH), and fibrosis. Angiotensin-II plays a major role in the development of uremic cardiomyopathy via nitro-oxidative and inflammatory mechanisms. In heart failure, the beta-3 adrenergic receptor (β3-AR) is up-regulated and coupled to endothelial nitric oxide synthase (eNOS)-mediated pathways, exerting antiremodeling effects. We aimed to compare the antiremodeling effects of the angiotensin-II receptor blocker losartan and the β3-AR agonist mirabegron in uremic cardiomyopathy. Chronic kidney disease (CKD) was induced by 5/6th nephrectomy in male Wistar rats. Five weeks later, rats were randomized into four groups: (1) sham-operated, (2) CKD, (3) losartan-treated (10 mg/kg/day) CKD, and (4) mirabegron-treated (10 mg/kg/day) CKD groups. At week 13, echocardiographic, histologic, laboratory, qRT-PCR, and Western blot measurements proved the development of uremic cardiomyopathy with DD, LVH, fibrosis, inflammation, and reduced eNOS levels, which were significantly ameliorated by losartan. However, mirabegron showed a tendency to decrease DD and fibrosis; but eNOS expression remained reduced. In uremic cardiomyopathy, β3-AR, sarcoplasmic reticulum ATPase (SERCA), and phospholamban levels did not change irrespective of treatments. Mirabegron reduced the angiotensin-II receptor 1 expression in uremic cardiomyopathy that might explain its mild antiremodeling effects despite the unchanged expression of the β3-AR.
format	article
author	Zsuzsanna Z. A. Kovács Gergő Szűcs Marah Freiwan Mónika G. Kovács Fanni M. Márványkövi Hoa Dinh Andrea Siska Katalin Farkas Ferenc Kovács András Kriston Péter Horváth Bence Kővári Bálint Gábor Cserni Gábor Cserni Imre Földesi Tamás Csont Márta Sárközy
author_facet	Zsuzsanna Z. A. Kovács Gergő Szűcs Marah Freiwan Mónika G. Kovács Fanni M. Márványkövi Hoa Dinh Andrea Siska Katalin Farkas Ferenc Kovács András Kriston Péter Horváth Bence Kővári Bálint Gábor Cserni Gábor Cserni Imre Földesi Tamás Csont Márta Sárközy
author_sort	Zsuzsanna Z. A. Kovács
title	Comparison of the antiremodeling effects of losartan and mirabegron in a rat model of uremic cardiomyopathy
title_short	Comparison of the antiremodeling effects of losartan and mirabegron in a rat model of uremic cardiomyopathy
title_full	Comparison of the antiremodeling effects of losartan and mirabegron in a rat model of uremic cardiomyopathy
title_fullStr	Comparison of the antiremodeling effects of losartan and mirabegron in a rat model of uremic cardiomyopathy
title_full_unstemmed	Comparison of the antiremodeling effects of losartan and mirabegron in a rat model of uremic cardiomyopathy
title_sort	comparison of the antiremodeling effects of losartan and mirabegron in a rat model of uremic cardiomyopathy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3ad90176f4df4c6c9713c509cda2b33c
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Comparison of the antiremodeling effects of losartan and mirabegron in a rat model of uremic cardiomyopathy

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