Cargando…

Hypertensive Effect of Downregulation of the Opioid System in Mouse Model of Different Activity of the Endogenous Opioid System

The opioid system is well-known for its role in modulating nociception and addiction development. However, there are premises that the endogenous opioid system may also affect blood pressure. The main goal of the present study was to determine the impact of different endogenous opioid system activit...

Descripción completa

Detalles Bibliográficos
Autores principales: Skiba, Dominik S., Szczepaniak, Piotr, Siedliński, Mateusz, Poznański, Piotr, Łazarczyk, Marzena, Jaskuła, Kinga, Religa, Piotr, Sacharczuk, Mariusz, Gaciong, Zbigniew
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073468/
https://www.ncbi.nlm.nih.gov/pubmed/33920718
http://dx.doi.org/10.3390/ijms22084179
_version_ 1783684137080586240
author Skiba, Dominik S.
Szczepaniak, Piotr
Siedliński, Mateusz
Poznański, Piotr
Łazarczyk, Marzena
Jaskuła, Kinga
Religa, Piotr
Sacharczuk, Mariusz
Gaciong, Zbigniew
author_facet Skiba, Dominik S.
Szczepaniak, Piotr
Siedliński, Mateusz
Poznański, Piotr
Łazarczyk, Marzena
Jaskuła, Kinga
Religa, Piotr
Sacharczuk, Mariusz
Gaciong, Zbigniew
author_sort Skiba, Dominik S.
collection PubMed
description The opioid system is well-known for its role in modulating nociception and addiction development. However, there are premises that the endogenous opioid system may also affect blood pressure. The main goal of the present study was to determine the impact of different endogenous opioid system activity and its pharmacological blockade on blood pressure. Moreover, we examined the vascular function in hyper- and hypoactive states of the opioid system and its pharmacological modification. In our study, we used two mouse lines which are divergently bred for high (HA) and low (LA) swim stress-induced analgesia. The obtained results indicated that individuals with low endogenous opioid system activity have higher basal blood pressure compared to those with a hyperactive opioid system. Additionally, naloxone administration only resulted in the elevation of blood pressure in HA mice. We also showed that the hypoactive opioid system contributes to impaired vascular relaxation independent of endothelium, which corresponded with decreased guanylyl cyclase levels in the aorta. Together, these data suggest that higher basal blood pressure in LA mice is a result of disturbed mechanisms in vascular relaxation in smooth muscle cells. We believe that a novel mechanism which involves endogenous opioid system activity in the regulation of blood pressure will be a promising target for further studies in hypertension development.
format Online
Article
Text
id pubmed-8073468
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-80734682021-04-27 Hypertensive Effect of Downregulation of the Opioid System in Mouse Model of Different Activity of the Endogenous Opioid System Skiba, Dominik S. Szczepaniak, Piotr Siedliński, Mateusz Poznański, Piotr Łazarczyk, Marzena Jaskuła, Kinga Religa, Piotr Sacharczuk, Mariusz Gaciong, Zbigniew Int J Mol Sci Article The opioid system is well-known for its role in modulating nociception and addiction development. However, there are premises that the endogenous opioid system may also affect blood pressure. The main goal of the present study was to determine the impact of different endogenous opioid system activity and its pharmacological blockade on blood pressure. Moreover, we examined the vascular function in hyper- and hypoactive states of the opioid system and its pharmacological modification. In our study, we used two mouse lines which are divergently bred for high (HA) and low (LA) swim stress-induced analgesia. The obtained results indicated that individuals with low endogenous opioid system activity have higher basal blood pressure compared to those with a hyperactive opioid system. Additionally, naloxone administration only resulted in the elevation of blood pressure in HA mice. We also showed that the hypoactive opioid system contributes to impaired vascular relaxation independent of endothelium, which corresponded with decreased guanylyl cyclase levels in the aorta. Together, these data suggest that higher basal blood pressure in LA mice is a result of disturbed mechanisms in vascular relaxation in smooth muscle cells. We believe that a novel mechanism which involves endogenous opioid system activity in the regulation of blood pressure will be a promising target for further studies in hypertension development. MDPI 2021-04-17 /pmc/articles/PMC8073468/ /pubmed/33920718 http://dx.doi.org/10.3390/ijms22084179 Text en © 2021 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
Skiba, Dominik S.
Szczepaniak, Piotr
Siedliński, Mateusz
Poznański, Piotr
Łazarczyk, Marzena
Jaskuła, Kinga
Religa, Piotr
Sacharczuk, Mariusz
Gaciong, Zbigniew
Hypertensive Effect of Downregulation of the Opioid System in Mouse Model of Different Activity of the Endogenous Opioid System
title Hypertensive Effect of Downregulation of the Opioid System in Mouse Model of Different Activity of the Endogenous Opioid System
title_full Hypertensive Effect of Downregulation of the Opioid System in Mouse Model of Different Activity of the Endogenous Opioid System
title_fullStr Hypertensive Effect of Downregulation of the Opioid System in Mouse Model of Different Activity of the Endogenous Opioid System
title_full_unstemmed Hypertensive Effect of Downregulation of the Opioid System in Mouse Model of Different Activity of the Endogenous Opioid System
title_short Hypertensive Effect of Downregulation of the Opioid System in Mouse Model of Different Activity of the Endogenous Opioid System
title_sort hypertensive effect of downregulation of the opioid system in mouse model of different activity of the endogenous opioid system
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073468/
https://www.ncbi.nlm.nih.gov/pubmed/33920718
http://dx.doi.org/10.3390/ijms22084179
work_keys_str_mv AT skibadominiks hypertensiveeffectofdownregulationoftheopioidsysteminmousemodelofdifferentactivityoftheendogenousopioidsystem
AT szczepaniakpiotr hypertensiveeffectofdownregulationoftheopioidsysteminmousemodelofdifferentactivityoftheendogenousopioidsystem
AT siedlinskimateusz hypertensiveeffectofdownregulationoftheopioidsysteminmousemodelofdifferentactivityoftheendogenousopioidsystem
AT poznanskipiotr hypertensiveeffectofdownregulationoftheopioidsysteminmousemodelofdifferentactivityoftheendogenousopioidsystem
AT łazarczykmarzena hypertensiveeffectofdownregulationoftheopioidsysteminmousemodelofdifferentactivityoftheendogenousopioidsystem
AT jaskułakinga hypertensiveeffectofdownregulationoftheopioidsysteminmousemodelofdifferentactivityoftheendogenousopioidsystem
AT religapiotr hypertensiveeffectofdownregulationoftheopioidsysteminmousemodelofdifferentactivityoftheendogenousopioidsystem
AT sacharczukmariusz hypertensiveeffectofdownregulationoftheopioidsysteminmousemodelofdifferentactivityoftheendogenousopioidsystem
AT gaciongzbigniew hypertensiveeffectofdownregulationoftheopioidsysteminmousemodelofdifferentactivityoftheendogenousopioidsystem