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

Dominik S Skiba,Piotr Poznański,Kinga Jaskuła,Mateusz Siedliński,Piotr Religa,Marzena Łazarczyk,Zbigniew Gaciong,Piotr Szczepaniak,Mariusz Sacharczuk

doi:10.3390/ijms22084179

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.

Highlights

Mice selected for high (HA) and low (LA) swim stress-induced analgesia (SSIA) are characterized by unique, inherited differences in opioid system activity [18]
The latency of HA mice measured by the Hot plate (HP) test after swimming was elevated, reaching the maximum value after 5 min in comparison to LA mice
LA mice were characterized with a constant latency time throughout the whole period (Figure 1b)

Summary

Introduction

The endogenous opioid system has long been almost exclusively concerned with its effects on analgesic and antinociceptive phenomena [1]. It was found relatively early that exogenous opioids may exert potent cardiorespiratory effects [2]. The role of opioid peptides in the autonomic regulation of blood pressure, heart function, and respiration became even more complex [3]. Opioids may be cardioprotective by attenuating ischemic reperfusion injury and decreasing apoptosis in myocytes, causing smaller infarct and ameliorating ventricular function [4].

Objectives

Methods

Results

Conclusion