Aims: Long-term
salt diet induces the oxidative stress in the paraventricular nucleus (PVN) and increases the blood pressure. Extracellular
superoxide dismutase (Ec-SOD) is a unique
antioxidant enzyme that exists in extracellular space and plays an essential role in scavenging excessive
reactive oxygen species (ROS). However, the underlying mechanism of Ec-SOD in the PVN remains unclear. Methods: Sprague-Dawley rats (150-200 g) were fed either a high
salt diet (8% NaCl, HS) or normal
salt diet (
0.9% NaCl, NS) for 6 weeks. Each group of rats was administered with bilateral PVN microinjection of AAV-Ec-SOD (Ec-SOD overexpression) or AAV-Ctrl for the next 6 weeks. Results: High
salt intake not only increased mean arterial blood pressure (MAP) and the plasma
noradrenaline (NE) but also elevated the
NAD(P)H oxidase activity, the
NAD(P)H oxidase components (NOX2 and NOX4) expression, and ROS production in the PVN. Meanwhile, the
NOD-like receptor protein 3 (NLRP3)-dependent inflammatory
proteins (ASC, pro-cas-1, IL-β, CXCR, CCL2) expression and the
tyrosine hydroxylase (TH) expression in the PVN with high
salt diet were higher, but the GSH level, Ec-SOD activity, GAD67 expression, and
GABA level were lower than the NS group. Bilateral PVN microinjection of AAV-Ec-SOD decreased MAP and the plasma NE, reduced
NAD(P)H oxidase activity, the NOX2 and NOX4 expression, and ROS production, attenuated NLRP3-dependent inflammatory expression and TH, but increased GSH level, Ec-SOD activity, GAD67 expression, and
GABA level in the PVN compared with the high
salt group. Conclusion: Excessive
salt intake not only activates oxidative stress but also induces the NLRP3-depensent
inflammation and breaks the balance between inhibitory and excitability
neurotransmitters in the PVN. Ec-SOD, as an essential anti-oxidative
enzyme, eliminates the ROS in the PVN and decreases the blood pressure, probably through inhibiting the NLRP3-dependent
inflammation and improving the excitatory
neurotransmitter release in the PVN in the
salt-induced
hypertension.