Hypertensive effect of downregulation of the opioid system in mouse model of different activity of the endogenous opioid system

Skiba, D. S., Szczepaniak, P., Siedliński, M., Poznański, P., Łazarczyk, M., Jaskuła, K., Religa, P., Sacharczuk, M. and Gaciong, Z. (2021) Hypertensive effect of downregulation of the opioid system in mouse model of different activity of the endogenous opioid system. International Journal of Molecular Sciences, 22(8), 4179. (doi: 10.3390/ijms22084179) (PMID:33920718) (PMCID:PMC8073468)

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Abstract

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.

Item Type:Articles
Additional Information:This work was supported by National Science Centre, Poland, project number 2019/35/D/ NZ5/02820 and 2014/15/B/NZ5/03566.
Keywords:Opioid system, vascular function, guanylyl cyclase, blood pressure.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Szczepaniak, Mr Piotr and Siedlinski, Mr Mateusz and Skiba, Mr Dominik
Creator Roles:
Skiba, D. S.Conceptualization, Methodology, Software, Validation, Formal analysis, Investigation, Resources, Data curation, Writing – original draft, Writing – review and editing, Visualization, Supervision, Funding acquisition
Szczepaniak, P.Methodology, Validation, Writing – review and editing
Siedliński, M.Methodology, Software, Formal analysis, Resources, Writing – review and editing
Authors: Skiba, D. S., Szczepaniak, P., Siedliński, M., Poznański, P., Łazarczyk, M., Jaskuła, K., Religa, P., Sacharczuk, M., and Gaciong, Z.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:International Journal of Molecular Sciences
Publisher:MDPI
ISSN:1661-6596
ISSN (Online):1422-0067
Published Online:17 April 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in International Journal of Molecular Sciences 22(8): 4179
Publisher Policy:Reproduced under a Creative Commons License

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