Key result
PVN infusion of minocycline attenuated high salt-induced elevations in mean arterial pressure, sympathetic nerve activity, and inflammatory and oxidative stress markers in Dahl salt-sensitive rats.
Why the study?
Activated microglia releasing proinflammatory cytokines contribute to cardiovascular disease progression, but whether high salt-induced hypothalamic paraventricular nucleus microglial activation increases oxidative stress, sympathoexcitation, and hypertension remained to be tested.
Does PVN infusion of minocycline reduce mean arterial pressure and sympathoexcitation in male Dahl salt-sensitive rats on a high-salt diet?
Does PVN infusion of minocycline reduce mean arterial pressure and sympathoexcitation in male Dahl salt-sensitive rats on a high-salt diet?
Blockade of microglial activation in the PVN with minocycline attenuates high salt-induced hypertension, sympathoexcitation, inflammation, and oxidative stress in Dahl salt-sensitive rats.
Hypothesis-generating for PVN microglial blockade in salt-sensitive hypertension; prospective human studies required before clinical consideration.
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 hypothalamic paraventricular nucleus (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 and central prostaglandin E2, as well as increase of plasma norepinephrine, were observed in those hypertensive rats. Tumor necrosis factor-α, interleukin-1β (IL-1β), and 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 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.
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Yu et al. (2022) studied High salt-induced hypertension. PVN infusion of minocycline vs. artificial cerebrospinal fluid was evaluated on Mean arterial pressure and sympathetic nerve activity. PVN infusion of minocycline attenuated high salt-induced elevations in mean arterial pressure, sympathetic nerve activity, and inflammatory and oxidative stress markers in Dahl salt-sensitive rats.
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