Blockade of Endogenous Angiotensin-(1-7) in Hypothalamic Paraventricular Nucleus Attenuates High Salt-Induced Sympathoexcitation and Hypertension.
- Author:
Xiao-Jing YU
1
;
Yu-Wang MIAO
1
;
Hong-Bao LI
1
;
Qing SU
1
;
Kai-Li LIU
1
;
Li-Yan FU
1
;
Yi-Kang HOU
2
;
Xiao-Lian SHI
3
;
Ying LI
1
;
Jian-Jun MU
4
;
Wen-Sheng CHEN
5
;
Wei CUI
6
;
Guo-Qing ZHU
7
;
Philip J EBENEZER
8
;
Joseph FRANCIS
9
;
Yu-Ming KANG
10
Author Information
- Publication Type:Journal Article
- Keywords: Angiotensin-(1–7); High-salt diet; Hypertension; Paraventricular nucleus; Pro-inflammatory cytokines
- MeSH: Angiotensin I; antagonists & inhibitors; metabolism; Animals; Antioxidants; pharmacology; Blood Pressure; drug effects; Hypertension; chemically induced; drug therapy; Male; Oxidative Stress; drug effects; Paraventricular Hypothalamic Nucleus; drug effects; Peptide Fragments; antagonists & inhibitors; metabolism; Rats, Sprague-Dawley; Reactive Oxygen Species; metabolism; Sodium Chloride, Dietary; pharmacology
- From:Neuroscience Bulletin 2019;35(1):47-56
- CountryChina
- Language:English
- Abstract: Angiotensin (Ang)-(1-7) is an important biologically-active peptide of the renin-angiotensin system. This study was designed to determine whether inhibition of Ang-(1-7) in the hypothalamic paraventricular nucleus (PVN) attenuates sympathetic activity and elevates blood pressure by modulating pro-inflammatory cytokines (PICs) and oxidative stress in the PVN in salt-induced hypertension. Rats were fed either a high-salt (8% NaCl) or a normal salt diet (0.3% NaCl) for 10 weeks, followed by bilateral microinjections of the Ang-(1-7) antagonist A-779 or vehicle into the PVN. We found that the mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma norepinephrine (NE) were significantly increased in salt-induced hypertensive rats. The high-salt diet also resulted in higher levels of the PICs interleukin-6, interleukin-1beta, tumor necrosis factor alpha, and monocyte chemotactic protein-1, as well as higher gp91 expression and superoxide production in the PVN. Microinjection of A-779 (3 nmol/50 nL) into the bilateral PVN of hypertensive rats not only attenuated MAP, RSNA, and NE, but also decreased the PICs and oxidative stress in the PVN. These results suggest that the increased MAP and sympathetic activity in salt-induced hypertension can be suppressed by blockade of endogenous Ang-(1-7) in the PVN, through modulation of PICs and oxidative stress.
