Central blockade of salusin β attenuates hypertension and hypothalamic inflammation in spontaneously hypertensive rats

Hong-Bao Li; Da-Nian Qin; Kang Cheng; Qing Su; Yu-Wang Miao; Jing Guo; Meng Zhang; Guo-Qing Zhu; Yu-Ming Kang

doi:10.1038/srep11162

Central blockade of salusin β attenuates hypertension and hypothalamic inflammation in spontaneously hypertensive rats

Sci Rep. 2015 Jul 29:5:11162. doi: 10.1038/srep11162.

Authors

Hong-Bao Li¹, Da-Nian Qin², Kang Cheng³, Qing Su¹, Yu-Wang Miao¹, Jing Guo¹, Meng Zhang¹, Guo-Qing Zhu⁴, Yu-Ming Kang¹

Affiliations

¹ Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
² Department of Physiology, Shantou University Medical College, Shantou 515041, China.
³ Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
⁴ Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029, China.

Abstract

Salusin β is a multifunctional bioactive peptide and is considered as a promising candidate biomarker for predicting atherosclerotic cardiovascular diseases. The present study was designed to investigate the roles and mechanisms of salusin β in the paraventricular nucleus (PVN) in attenuating hypertension and hypothalamic inflammation and whether central salusin β blockade has protective effects in essential hypertension. Normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were used in this study. The rats were chronic PVN infusion either specific salusin β blocker, antisalusin β IgG (SIgG), or control IgG (CIgG) for 2 weeks. Hypertensive rats had significantly increased salusin β expression compared with normotensive rats. Central blockade of salusin β attenuated hypertension, reduced circulating norepinephrine (NE) levels, and improved cardiac hypertrophy and function in hypertensive rats. Salusin β blockade significantly reduced proinflammatory cytokines (PICs), nuclear factor-kappa B (NF-κB) activity, reactive oxygen species (ROS) levels, and altered renin-angiotensin system (RAS) components in the PVN of hypertensive rats. These findings suggest that the beneficial effects of salusin β blockade in essential hypertension are possibly due to down-regulate of inflammatory molecules and ROS in the PVN.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Monoclonal / pharmacology
Blood Pressure / drug effects
Cardiomegaly / diagnosis
Cardiomegaly / drug therapy
Cardiomegaly / etiology
Cytokines / metabolism
Essential Hypertension
Heart Rate / drug effects
Hypertension / etiology*
Hypertension / metabolism*
Hypertension / physiopathology
Hypothalamus / drug effects
Hypothalamus / metabolism*
Hypothalamus / pathology
Immunoglobulin G / pharmacology
Inflammation / drug therapy
Inflammation / metabolism*
Inflammation Mediators / metabolism
Intercellular Signaling Peptides and Proteins / metabolism*
Male
Membrane Glycoproteins / genetics
Membrane Glycoproteins / metabolism
NADPH Oxidase 2
NADPH Oxidases / genetics
NADPH Oxidases / metabolism
NF-kappa B / metabolism
Oxidative Stress / drug effects
Paraventricular Hypothalamic Nucleus / drug effects
Paraventricular Hypothalamic Nucleus / metabolism
Peptidyl-Dipeptidase A / genetics
Peptidyl-Dipeptidase A / metabolism
Rats
Rats, Inbred SHR
Reactive Oxygen Species / metabolism

Substances

Antibodies, Monoclonal
Cytokines
Immunoglobulin G
Inflammation Mediators
Intercellular Signaling Peptides and Proteins
Membrane Glycoproteins
NF-kappa B
Reactive Oxygen Species
salusin-beta, rat
Cybb protein, rat
NADPH Oxidase 2
NADPH Oxidases
Peptidyl-Dipeptidase A