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Chronic Naltrexone Therapy Is Associated with Improved Cardiac Function in Volume Overloaded Rats

PURPOSE: Myocardial opioid receptors were demonstrated in animals and humans and seem to colocalize with membranous and sarcolemmal calcium channels of the excitation–contraction coupling in the left ventricle (LV). Therefore, this study investigated whether blockade of the cardiac opioid system by...

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Autores principales: Dehe, Lukas, Shaqura, Mohammed, Nordine, Michael, Habazettl, Helmut, von Kwiatkowski, Petra, Schluchter, Helena, Shakibaei, Mehdi, Mousa, Shaaban A., Schäfer, Michael, Treskatsch, Sascha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266787/
https://www.ncbi.nlm.nih.gov/pubmed/33484395
http://dx.doi.org/10.1007/s10557-020-07132-4
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author Dehe, Lukas
Shaqura, Mohammed
Nordine, Michael
Habazettl, Helmut
von Kwiatkowski, Petra
Schluchter, Helena
Shakibaei, Mehdi
Mousa, Shaaban A.
Schäfer, Michael
Treskatsch, Sascha
author_facet Dehe, Lukas
Shaqura, Mohammed
Nordine, Michael
Habazettl, Helmut
von Kwiatkowski, Petra
Schluchter, Helena
Shakibaei, Mehdi
Mousa, Shaaban A.
Schäfer, Michael
Treskatsch, Sascha
author_sort Dehe, Lukas
collection PubMed
description PURPOSE: Myocardial opioid receptors were demonstrated in animals and humans and seem to colocalize with membranous and sarcolemmal calcium channels of the excitation–contraction coupling in the left ventricle (LV). Therefore, this study investigated whether blockade of the cardiac opioid system by naltrexone would affect cardiac function and neurohumoral parameters in Wistar rats with volume overload-induced heart failure. METHODS: Volume overload in Wistar rats was induced by an aortocaval fistula (ACF). Left ventricular cardiac opioid receptors were identified by immunohistochemistry and their messenger ribonucleic acid (mRNA) as well as their endogenous ligand mRNA quantified by real-time polymerase chain reaction (RT-PCR). Following continuous delivery of either the opioid receptor antagonist naltrexone or vehicle via minipumps (n = 5 rats each), hemodynamic and humoral parameters were assessed 28 days after ACF induction. Sham-operated animals served as controls. RESULTS: In ACF rats mu-, delta-, and kappa-opioid receptors colocalized with voltage-gated L-type Ca2+ channels in left ventricular cardiomyocytes. Chronic naltrexone treatment of ACF rats reduced central venous pressure (CVP) and left ventricular end-diastolic pressure (LVEDP), and improved systolic and diastolic left ventricular functions. Concomitantly, rat brain natriuretic peptide (rBNP-45) and angiotensin-2 plasma concentrations which were elevated during ACF were significantly diminished following naltrexone treatment. In parallel, chronic naltrexone significantly reduced mu-, delta-, and kappa-opioid receptor mRNA, while it increased the endogenous opioid peptide mRNA compared to controls. CONCLUSION: Opioid receptor blockade by naltrexone leads to improved LV function and decreases in rBNP-45 and angiotensin-2 plasma levels. In parallel, naltrexone resulted in opioid receptor mRNA downregulation and an elevated intrinsic tone of endogenous opioid peptides possibly reflecting a potentially cardiodepressant effect of the cardiac opioid system during volume overload.
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spelling pubmed-82667872021-07-20 Chronic Naltrexone Therapy Is Associated with Improved Cardiac Function in Volume Overloaded Rats Dehe, Lukas Shaqura, Mohammed Nordine, Michael Habazettl, Helmut von Kwiatkowski, Petra Schluchter, Helena Shakibaei, Mehdi Mousa, Shaaban A. Schäfer, Michael Treskatsch, Sascha Cardiovasc Drugs Ther Routine Article PURPOSE: Myocardial opioid receptors were demonstrated in animals and humans and seem to colocalize with membranous and sarcolemmal calcium channels of the excitation–contraction coupling in the left ventricle (LV). Therefore, this study investigated whether blockade of the cardiac opioid system by naltrexone would affect cardiac function and neurohumoral parameters in Wistar rats with volume overload-induced heart failure. METHODS: Volume overload in Wistar rats was induced by an aortocaval fistula (ACF). Left ventricular cardiac opioid receptors were identified by immunohistochemistry and their messenger ribonucleic acid (mRNA) as well as their endogenous ligand mRNA quantified by real-time polymerase chain reaction (RT-PCR). Following continuous delivery of either the opioid receptor antagonist naltrexone or vehicle via minipumps (n = 5 rats each), hemodynamic and humoral parameters were assessed 28 days after ACF induction. Sham-operated animals served as controls. RESULTS: In ACF rats mu-, delta-, and kappa-opioid receptors colocalized with voltage-gated L-type Ca2+ channels in left ventricular cardiomyocytes. Chronic naltrexone treatment of ACF rats reduced central venous pressure (CVP) and left ventricular end-diastolic pressure (LVEDP), and improved systolic and diastolic left ventricular functions. Concomitantly, rat brain natriuretic peptide (rBNP-45) and angiotensin-2 plasma concentrations which were elevated during ACF were significantly diminished following naltrexone treatment. In parallel, chronic naltrexone significantly reduced mu-, delta-, and kappa-opioid receptor mRNA, while it increased the endogenous opioid peptide mRNA compared to controls. CONCLUSION: Opioid receptor blockade by naltrexone leads to improved LV function and decreases in rBNP-45 and angiotensin-2 plasma levels. In parallel, naltrexone resulted in opioid receptor mRNA downregulation and an elevated intrinsic tone of endogenous opioid peptides possibly reflecting a potentially cardiodepressant effect of the cardiac opioid system during volume overload. Springer US 2021-01-23 2021 /pmc/articles/PMC8266787/ /pubmed/33484395 http://dx.doi.org/10.1007/s10557-020-07132-4 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Routine Article
Dehe, Lukas
Shaqura, Mohammed
Nordine, Michael
Habazettl, Helmut
von Kwiatkowski, Petra
Schluchter, Helena
Shakibaei, Mehdi
Mousa, Shaaban A.
Schäfer, Michael
Treskatsch, Sascha
Chronic Naltrexone Therapy Is Associated with Improved Cardiac Function in Volume Overloaded Rats
title Chronic Naltrexone Therapy Is Associated with Improved Cardiac Function in Volume Overloaded Rats
title_full Chronic Naltrexone Therapy Is Associated with Improved Cardiac Function in Volume Overloaded Rats
title_fullStr Chronic Naltrexone Therapy Is Associated with Improved Cardiac Function in Volume Overloaded Rats
title_full_unstemmed Chronic Naltrexone Therapy Is Associated with Improved Cardiac Function in Volume Overloaded Rats
title_short Chronic Naltrexone Therapy Is Associated with Improved Cardiac Function in Volume Overloaded Rats
title_sort chronic naltrexone therapy is associated with improved cardiac function in volume overloaded rats
topic Routine Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266787/
https://www.ncbi.nlm.nih.gov/pubmed/33484395
http://dx.doi.org/10.1007/s10557-020-07132-4
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