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Blockade of Microglial Activation in Hypothalamic Paraventricular Nucleus Improves High-salt Induced Hypertension.

BACKGROUND
It has been shown that activated microglia in brain releasing proinflammatory cytokines (PICs) contribute to the progression of cardiovascular diseases. In this study, we tested the hypothesis that microglial activation in paraventricular nucleus of hypothalamus (PVN), induced by high-salt diet, increases the oxidative stress via releasing PICs, and promotes sympathoexcitation and development of hypertension.


METHODS
High-salt diet was given to male Dahl salt-sensitive rats to induce hypertension. Those rats were bilaterally implanted with cannula for PVN infusion of minocycline, a selective microglial activation blocker, or artificial cerebrospinal fluid for 4 weeks.


RESULTS
High-salt diet elevated mean arterial pressure of Dahl salt-sensitive rats. Meanwhile, elevations of renal sympathetic nerve activity (RSNA) and central prostaglandin E2(PGE2), as well as increase of plasma norepinephrine, were observed in those hypertensive rats. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) increased in the PVN of those rats, associated with a significant activation of microglia and prominent disruption of redox balance, which was demonstrated by higher superoxide and NAD(P)H oxidase 2 (NOX-2) and NAD(P)H oxidase 4 (NOX-4), and lower Cu/Zn superoxide dismutase (Cu/Zn-SOD) in PVN. PVN infusion of minocycline attenuated all hypertension-related alterations described above.


CONCLUSION
This study indicates that high-salt leads to microglial activation within PVN of hypertensive rats, and those activated PVN microglia release PICs and trigger the production of reactive oxygen species, which contributes to sympathoexcitation and development of hypertension. Blockade of PVN microglial activation inhibits inflammation and oxidative stress, therefore attenuating the development of hypertension induced by high-salt diet.