NF-κB Blockade in Hypothalamic Paraventricular Nucleus Inhibits High-Salt-Induced Hypertension Through NLRP3 and Caspase-1
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- 作者：Jie Qi ; Xiao-Jing Yu ; Xiao-Lian Shi ; Hong-Li Gao ; Qiu-Yue Yi…
- 关键词：Salt ; sensitive hypertension ; NLRP3 ; NF ; κB ; Hypothalamic paraventricular nucleus ; Oxidative stress
- 刊名：Cardiovascular Toxicology
- 出版年：2016
- 出版时间：October 2016
- 年：2016
- 卷：16
- 期：4
- 页码：345-354
- 全文大小：1,214 KB
- 刊物主题：Pharmacology/Toxicology; Cardiology;
- 出版者：Springer US
- ISSN：1559-0259
- 卷排序：16
文摘
High-salt-induced inflammation and oxidative stress in the hypothalamic paraventricular nucleus (PVN) contribute to the pathogenesis of salt-sensitive hypertension. In this study, we hypothesized that chronic inhibition of nuclear factor-κB (NF-κB) activity in the PVN delays the progression of hypertension by upregulating anti-inflammatory cytokines, reducing NLRP3 (NOD-like receptor family pyrin domain containing 3) and IL-1β and attenuating p-IKKβ, NF-κB p65 activity and NAD(P)H oxidase in the PVN of salt-sensitive hypertensive rats. Dahl salt-sensitive rats received a high-salt diet (HS, 8 % NaCl) or a normal-salt diet (NS, 0.3 % NaCl) for 6 weeks and were treated with bilateral PVN infusion with either vehicle or pyrrolidine dithiocarbamate (PDTC, 5 μg/h), a NF-κB inhibitor via osmotic minipump. The mean arterial pressure and plasma levels of norepinephrine (NE) and epinephrine (EPI) were significantly increased in high-salt-fed rats. In addition, rats with high-salt diet had higher levels of p-IKKβ, NF-κB p65 activity, Fra-like (Fra-LI) activity (an indicator of chronic neuronal activation), NOX-4 (subunits of NAD(P)H oxidase), NLRP3 and IL-1β, and lower levels of IL-10 in the PVN than normal diet rats. Bilateral PVN infusions of PDTC attenuated these high-salt-induced changes. These findings suggest that high-salt-induced NF-κB activation in the PVN caused hypertension via sympathoexcitation, which are associated with the increases of NLRP3, IL-1β and oxidative stress in the PVN; PVN inhibition of NF-κB activity attenuates NLRP3, IL-1β and oxidative stress in the PVN and thereby attenuates hypertension.