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Sacubitril/Valsartan and Ivabradine Attenuate Left Ventricular Remodelling and Dysfunction in Spontaneously Hypertensive Rats: Different Interactions with the Renin–Angiotensin–Aldosterone System

This study investigated whether sacubitril/valsartan and ivabradine are able to prevent left ventricular (LV) fibrotic remodelling and dysfunction in a rat experimental model of spontaneous hypertension (spontaneously hypertensive rats, SHRs) and whether this potential protection is associated with...

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Autores principales: Simko, Fedor, Baka, Tomas, Stanko, Peter, Repova, Kristina, Krajcirovicova, Kristina, Aziriova, Silvia, Domenig, Oliver, Zorad, Stefan, Adamcova, Michaela, Paulis, Ludovit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9405404/
https://www.ncbi.nlm.nih.gov/pubmed/36009391
http://dx.doi.org/10.3390/biomedicines10081844
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author Simko, Fedor
Baka, Tomas
Stanko, Peter
Repova, Kristina
Krajcirovicova, Kristina
Aziriova, Silvia
Domenig, Oliver
Zorad, Stefan
Adamcova, Michaela
Paulis, Ludovit
author_facet Simko, Fedor
Baka, Tomas
Stanko, Peter
Repova, Kristina
Krajcirovicova, Kristina
Aziriova, Silvia
Domenig, Oliver
Zorad, Stefan
Adamcova, Michaela
Paulis, Ludovit
author_sort Simko, Fedor
collection PubMed
description This study investigated whether sacubitril/valsartan and ivabradine are able to prevent left ventricular (LV) fibrotic remodelling and dysfunction in a rat experimental model of spontaneous hypertension (spontaneously hypertensive rats, SHRs) and whether this potential protection is associated with RAAS alterations. Five groups of three-month-old male Wistar rats and SHRs were treated for six weeks as follows: untreated Wistar controls, Wistar plus sacubitril/valsartan, SHR, SHR plus sacubitril/valsartan, and SHR plus ivabradine. The SHRs developed a systolic blood pressure (SBP) increase, LV hypertrophy and fibrosis, and LV systolic and diastolic dysfunction. However, no changes in serum RAAS were observed in SHRs compared with the controls. Elevated SBP in SHRs was decreased by sacubitril/valsartan but not by ivabradine, and only sacubitril/valsartan attenuated LV hypertrophy. Both sacubitril/valsartan and ivabradine reduced LV collagen content and attenuated LV systolic and diastolic dysfunction. Sacubitril/valsartan increased the serum levels of angiotensin (Ang) II, Ang III, Ang IV, Ang 1-5, Ang 1-7, and aldosterone, while ivabradine did not affect the RAAS. We conclude that the SHR is a normal-to-low serum RAAS model of experimental hypertension. While the protection of the hypertensive heart in SHRs by sacubitril/valsartan may be related to an Ang II blockade and the protective Ang 1-7, the benefits of ivabradine were not associated with RAAS modulation.
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spelling pubmed-94054042022-08-26 Sacubitril/Valsartan and Ivabradine Attenuate Left Ventricular Remodelling and Dysfunction in Spontaneously Hypertensive Rats: Different Interactions with the Renin–Angiotensin–Aldosterone System Simko, Fedor Baka, Tomas Stanko, Peter Repova, Kristina Krajcirovicova, Kristina Aziriova, Silvia Domenig, Oliver Zorad, Stefan Adamcova, Michaela Paulis, Ludovit Biomedicines Article This study investigated whether sacubitril/valsartan and ivabradine are able to prevent left ventricular (LV) fibrotic remodelling and dysfunction in a rat experimental model of spontaneous hypertension (spontaneously hypertensive rats, SHRs) and whether this potential protection is associated with RAAS alterations. Five groups of three-month-old male Wistar rats and SHRs were treated for six weeks as follows: untreated Wistar controls, Wistar plus sacubitril/valsartan, SHR, SHR plus sacubitril/valsartan, and SHR plus ivabradine. The SHRs developed a systolic blood pressure (SBP) increase, LV hypertrophy and fibrosis, and LV systolic and diastolic dysfunction. However, no changes in serum RAAS were observed in SHRs compared with the controls. Elevated SBP in SHRs was decreased by sacubitril/valsartan but not by ivabradine, and only sacubitril/valsartan attenuated LV hypertrophy. Both sacubitril/valsartan and ivabradine reduced LV collagen content and attenuated LV systolic and diastolic dysfunction. Sacubitril/valsartan increased the serum levels of angiotensin (Ang) II, Ang III, Ang IV, Ang 1-5, Ang 1-7, and aldosterone, while ivabradine did not affect the RAAS. We conclude that the SHR is a normal-to-low serum RAAS model of experimental hypertension. While the protection of the hypertensive heart in SHRs by sacubitril/valsartan may be related to an Ang II blockade and the protective Ang 1-7, the benefits of ivabradine were not associated with RAAS modulation. MDPI 2022-07-31 /pmc/articles/PMC9405404/ /pubmed/36009391 http://dx.doi.org/10.3390/biomedicines10081844 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Simko, Fedor
Baka, Tomas
Stanko, Peter
Repova, Kristina
Krajcirovicova, Kristina
Aziriova, Silvia
Domenig, Oliver
Zorad, Stefan
Adamcova, Michaela
Paulis, Ludovit
Sacubitril/Valsartan and Ivabradine Attenuate Left Ventricular Remodelling and Dysfunction in Spontaneously Hypertensive Rats: Different Interactions with the Renin–Angiotensin–Aldosterone System
title Sacubitril/Valsartan and Ivabradine Attenuate Left Ventricular Remodelling and Dysfunction in Spontaneously Hypertensive Rats: Different Interactions with the Renin–Angiotensin–Aldosterone System
title_full Sacubitril/Valsartan and Ivabradine Attenuate Left Ventricular Remodelling and Dysfunction in Spontaneously Hypertensive Rats: Different Interactions with the Renin–Angiotensin–Aldosterone System
title_fullStr Sacubitril/Valsartan and Ivabradine Attenuate Left Ventricular Remodelling and Dysfunction in Spontaneously Hypertensive Rats: Different Interactions with the Renin–Angiotensin–Aldosterone System
title_full_unstemmed Sacubitril/Valsartan and Ivabradine Attenuate Left Ventricular Remodelling and Dysfunction in Spontaneously Hypertensive Rats: Different Interactions with the Renin–Angiotensin–Aldosterone System
title_short Sacubitril/Valsartan and Ivabradine Attenuate Left Ventricular Remodelling and Dysfunction in Spontaneously Hypertensive Rats: Different Interactions with the Renin–Angiotensin–Aldosterone System
title_sort sacubitril/valsartan and ivabradine attenuate left ventricular remodelling and dysfunction in spontaneously hypertensive rats: different interactions with the renin–angiotensin–aldosterone system
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9405404/
https://www.ncbi.nlm.nih.gov/pubmed/36009391
http://dx.doi.org/10.3390/biomedicines10081844
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