Cargando…

Increased Endogenous Activity of the Renin-Angiotensin System Reduces Infarct Size in the Rats with Early Angiotensin II-dependent Hypertension which Survive the Acute Ischemia/Reperfusion Injury

We investigated the role of the interaction between hypertension and the renin-angiotensin system in the pathophysiology of myocardial ischemia/reperfusion injury. We hypothesized that in the early phase of angiotensin II (ANG II)-dependent hypertension with developed left ventricular hypertrophy, c...

Descripción completa

Detalles Bibliográficos
Autores principales: Husková, Zuzana, Kikerlová, Soňa, Sadowski, Janusz, Alánová, Petra, Sedláková, Lenka, Papoušek, František, Neckář, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193500/
https://www.ncbi.nlm.nih.gov/pubmed/34122103
http://dx.doi.org/10.3389/fphar.2021.679060
_version_ 1783706239497142272
author Husková, Zuzana
Kikerlová, Soňa
Sadowski, Janusz
Alánová, Petra
Sedláková, Lenka
Papoušek, František
Neckář, Jan
author_facet Husková, Zuzana
Kikerlová, Soňa
Sadowski, Janusz
Alánová, Petra
Sedláková, Lenka
Papoušek, František
Neckář, Jan
author_sort Husková, Zuzana
collection PubMed
description We investigated the role of the interaction between hypertension and the renin-angiotensin system in the pathophysiology of myocardial ischemia/reperfusion injury. We hypothesized that in the early phase of angiotensin II (ANG II)-dependent hypertension with developed left ventricular hypertrophy, cardioprotective mechanism(s) are fully activated. The experiments were performed in transgenic rats with inducible hypertension, noninduced rats served as controls. The early phase of ANG II-dependent hypertension was induced by five-days (5 days) dietary indole-3-carbinol administration. Cardiac hypertrophy, ANG II and ANG 1–7 levels, protein expression of their receptors and enzymes were determined. Separate groups were subjected to acute myocardial ischemia/reperfusion injury, and infarct size and ventricular arrhythmias were assessed. Induced rats developed marked cardiac hypertrophy accompanied by elevated ANG levels. Ischemia/reperfusion mortality was significantly higher in induced than noninduced rats (52.1 and 25%, respectively). The blockade of AT1 receptors with losartan significantly increased survival rate in both groups. Myocardial infarct size was significantly reduced after 5 days induction (by 11%), without changes after losartan treatment. In conclusion, we confirmed improved cardiac tolerance to ischemia/reperfusion injury in hypertensive cardiohypertrophied rats and found that activation of AT1 receptors by locally produced ANG II in the heart was not the mechanism underlying infarct size reduction.
format Online
Article
Text
id pubmed-8193500
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-81935002021-06-12 Increased Endogenous Activity of the Renin-Angiotensin System Reduces Infarct Size in the Rats with Early Angiotensin II-dependent Hypertension which Survive the Acute Ischemia/Reperfusion Injury Husková, Zuzana Kikerlová, Soňa Sadowski, Janusz Alánová, Petra Sedláková, Lenka Papoušek, František Neckář, Jan Front Pharmacol Pharmacology We investigated the role of the interaction between hypertension and the renin-angiotensin system in the pathophysiology of myocardial ischemia/reperfusion injury. We hypothesized that in the early phase of angiotensin II (ANG II)-dependent hypertension with developed left ventricular hypertrophy, cardioprotective mechanism(s) are fully activated. The experiments were performed in transgenic rats with inducible hypertension, noninduced rats served as controls. The early phase of ANG II-dependent hypertension was induced by five-days (5 days) dietary indole-3-carbinol administration. Cardiac hypertrophy, ANG II and ANG 1–7 levels, protein expression of their receptors and enzymes were determined. Separate groups were subjected to acute myocardial ischemia/reperfusion injury, and infarct size and ventricular arrhythmias were assessed. Induced rats developed marked cardiac hypertrophy accompanied by elevated ANG levels. Ischemia/reperfusion mortality was significantly higher in induced than noninduced rats (52.1 and 25%, respectively). The blockade of AT1 receptors with losartan significantly increased survival rate in both groups. Myocardial infarct size was significantly reduced after 5 days induction (by 11%), without changes after losartan treatment. In conclusion, we confirmed improved cardiac tolerance to ischemia/reperfusion injury in hypertensive cardiohypertrophied rats and found that activation of AT1 receptors by locally produced ANG II in the heart was not the mechanism underlying infarct size reduction. Frontiers Media S.A. 2021-05-28 /pmc/articles/PMC8193500/ /pubmed/34122103 http://dx.doi.org/10.3389/fphar.2021.679060 Text en Copyright © 2021 Husková, Kikerlová, Sadowski, Alánová, Sedláková, Papoušek and Neckář. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Husková, Zuzana
Kikerlová, Soňa
Sadowski, Janusz
Alánová, Petra
Sedláková, Lenka
Papoušek, František
Neckář, Jan
Increased Endogenous Activity of the Renin-Angiotensin System Reduces Infarct Size in the Rats with Early Angiotensin II-dependent Hypertension which Survive the Acute Ischemia/Reperfusion Injury
title Increased Endogenous Activity of the Renin-Angiotensin System Reduces Infarct Size in the Rats with Early Angiotensin II-dependent Hypertension which Survive the Acute Ischemia/Reperfusion Injury
title_full Increased Endogenous Activity of the Renin-Angiotensin System Reduces Infarct Size in the Rats with Early Angiotensin II-dependent Hypertension which Survive the Acute Ischemia/Reperfusion Injury
title_fullStr Increased Endogenous Activity of the Renin-Angiotensin System Reduces Infarct Size in the Rats with Early Angiotensin II-dependent Hypertension which Survive the Acute Ischemia/Reperfusion Injury
title_full_unstemmed Increased Endogenous Activity of the Renin-Angiotensin System Reduces Infarct Size in the Rats with Early Angiotensin II-dependent Hypertension which Survive the Acute Ischemia/Reperfusion Injury
title_short Increased Endogenous Activity of the Renin-Angiotensin System Reduces Infarct Size in the Rats with Early Angiotensin II-dependent Hypertension which Survive the Acute Ischemia/Reperfusion Injury
title_sort increased endogenous activity of the renin-angiotensin system reduces infarct size in the rats with early angiotensin ii-dependent hypertension which survive the acute ischemia/reperfusion injury
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193500/
https://www.ncbi.nlm.nih.gov/pubmed/34122103
http://dx.doi.org/10.3389/fphar.2021.679060
work_keys_str_mv AT huskovazuzana increasedendogenousactivityofthereninangiotensinsystemreducesinfarctsizeintheratswithearlyangiotensiniidependenthypertensionwhichsurvivetheacuteischemiareperfusioninjury
AT kikerlovasona increasedendogenousactivityofthereninangiotensinsystemreducesinfarctsizeintheratswithearlyangiotensiniidependenthypertensionwhichsurvivetheacuteischemiareperfusioninjury
AT sadowskijanusz increasedendogenousactivityofthereninangiotensinsystemreducesinfarctsizeintheratswithearlyangiotensiniidependenthypertensionwhichsurvivetheacuteischemiareperfusioninjury
AT alanovapetra increasedendogenousactivityofthereninangiotensinsystemreducesinfarctsizeintheratswithearlyangiotensiniidependenthypertensionwhichsurvivetheacuteischemiareperfusioninjury
AT sedlakovalenka increasedendogenousactivityofthereninangiotensinsystemreducesinfarctsizeintheratswithearlyangiotensiniidependenthypertensionwhichsurvivetheacuteischemiareperfusioninjury
AT papousekfrantisek increasedendogenousactivityofthereninangiotensinsystemreducesinfarctsizeintheratswithearlyangiotensiniidependenthypertensionwhichsurvivetheacuteischemiareperfusioninjury
AT neckarjan increasedendogenousactivityofthereninangiotensinsystemreducesinfarctsizeintheratswithearlyangiotensiniidependenthypertensionwhichsurvivetheacuteischemiareperfusioninjury