Salusin-β in Intermediate Dorsal Motor Nucleus of the Vagus Regulates Sympathetic-Parasympathetic Balance and Blood Pressure.

Lu-Lu Wu,Yue-Hua Li,Guo-Qing Zhu,Jin-Hua Bo,Fen Zheng,Feng Zhang,Yu-Ming Kang,Qi Chen

doi:10.3390/biomedicines9091118

Abstract

The dorsal motor nucleus of the vagus (DMV) is known to control vagal activity. It is unknown whether the DMV regulates sympathetic activity and whether salusin-β in the DMV contributes to autonomic nervous activity. We investigated the roles of salusin-β in DMV in regulating sympathetic-parasympathetic balance and its underline mechanisms. Microinjections were carried out in the DMV and hypothalamic paraventricular nucleus (PVN) in male adult anesthetized rats. Renal sympathetic nerve activity (RSNA), blood pressure and heart rate were recorded. Immunohistochemistry for salusin-β and reactive oxidative species (ROS) production in the DMV were examined. Salusin-β was expressed in the intermediate DMV (iDMV). Salusin-β in the iDMV not only inhibited RSNA but also enhanced vagal activity and thereby reduced blood pressure and heart rate. The roles of salusin-β in causing vagal activation were mediated by NAD(P)H oxidase-dependent superoxide anion production in the iDMV. The roles of salusin-β in inhibiting RSNA were mediated by not only the NAD(P)H oxidase-originated superoxide anion production in the iDMV but also the γ-aminobutyric acid (GABA)A receptor activation in PVN. Moreover, endogenous salusin-β and ROS production in the iDMV play a tonic role in inhibiting RSNA. These results indicate that salusin-β in the iDMV inhibits sympathetic activity and enhances vagal activity, and thereby reduces blood pressure and heart rate, which are mediated by NAD(P)H oxidase-dependent ROS production in the iDMV. Moreover, GABAA receptor in the PVN mediates the effect of salusin-β on sympathetic inhibition. Endogenous salusin-β and ROS production in the iDMV play a tonic role in inhibiting sympathetic activity.

Highlights

Microinjection of salusin-β in the nucleus of the solitary tract (NTS), intermediate reticular nucleus (IRN), hypoglossal nucleus (HN) and intermedius nucleus of medulla (INM) had no significant effects on the Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) (Figure 1E)
We firstly showed that salusin-β in the intermediate DMV (iDMV) regulated the balance between sympathetic activity and vagal activity
Neutralization of salusin-β with anti-salusin-β IgG increased sympathetic outflow and blood pressure, suggesting endogenous salusin-β in the iDMV plays a tonic role in inhibition of sympathetic activity

Summary

Introduction

Autonomic nervous system dysfunction is closely associated with cardiovascular diseases, including hypertension, chronic heart failure and chronic kidney disease [1,2,3]. Inhibition of the enhanced sympathetic activity such as renal denervation has been used as an important strategy for intervention of these diseases [4,5,6]. Many studies are focused on the roles and mechanisms of hypothalamic periventricular nucleus (PVN), rostral ventrolateral medulla (RVLM) and the nucleus of the solitary tract (NTS) in regulating. Biomedicines 2021, 9, 1118 sympathetic activity [7,8,9]. Interventions primarily aim to inhibit excessive sympathetic activation, while vagal activity has been largely neglected. The central control of the sympathetic-parasympathetic balance is not well elucidated

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