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

Abstract

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.

• Authors: Xiao-Jing Yu, Xiao-Jing Liu, Jing Guo, Yu-Kun Su, Nianping Zhang, Jie Qi, Ying Li, Li-Yan Fu, Kai-Li Liu, Yanjun Li, Yu-Ming Kang
• Journal: American journal of hypertension (Am J Hypertens) Vol. 35 Issue 9 Pg. 820-827 (09 01 2022) ISSN: 1941-7225 [Electronic] United States
• PMID: 35439285 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Cytokines
• Sodium Chloride, Dietary
• NADPH Oxidases
• Minocycline

Topics

• Animals
• Cytokines (metabolism)
• Hypertension
• Male
• Microglia (metabolism)
• Minocycline (adverse effects)
• NADPH Oxidases (metabolism)
• Paraventricular Hypothalamic Nucleus (metabolism)
• Rats
• Rats, Inbred Dahl
• Sodium Chloride, Dietary (adverse effects)