期刊
CARDIOVASCULAR TOXICOLOGY
卷 16, 期 4, 页码 345-354出版社
HUMANA PRESS INC
DOI: 10.1007/s12012-015-9344-9
关键词
Salt-sensitive hypertension; NLRP3; NF-kappa B; Hypothalamic paraventricular nucleus; Oxidative stress
资金
- National Basic Research Program of China [2012CB517805]
- National Natural Science Foundation of China [91439120, 81370356, 81170248, 81471471]
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-kappa B (NF-kappa B) 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-1 beta and attenuating p-IKK beta, NF-kappa B 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 mu g/h), a NF-kappa B 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-IKK beta, NF-kappa B p65 activity, Fra-like (Fra-LI) activity (an indicator of chronic neuronal activation), NOX-4 (subunits of NAD(P)H oxidase), NLRP3 and IL-1 beta, 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-kappa B activation in the PVN caused hypertension via sympathoexcitation, which are associated with the increases of NLRP3, IL-1 beta and oxidative stress in the PVN; PVN inhibition of NF-kappa B activity attenuates NLRP3, IL-1 beta and oxidative stress in the PVN and thereby attenuates hypertension.
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