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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurosci. | doi: 10.3389/fnins.2019.01138

Exercise training attenuates hypertension through TLR4/MyD88/NF-κB signaling in the hypothalamic paraventricular nucleus

Jie Qi1, Xiao-Jing Yu1, Li-Yan Fu1, Kai-Li Liu1, Kai B. Kang2, Ying Li1 and  Yu-Ming Kang1*
  • 1Department of Physiology and Pathophysiology, School of Basic Medical College, Xi'an Jiaotong University, China
  • 2Department of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois at Chicago, United States

Exercise training (ExT) is beneficial for cardiovascular health, yet the central mechanism by which ExT attenuates the hypertensive responses remains unclear. Activation of pro-inflammatory cytokines (PICs) in the hypothalamic paraventricular nucleus (PVN) is important for the sympathoexcitation and hypertensive response. We thus hypothesized that ExT can decrease the blood pressure of hypertensive rats by reducing the levels of PICs through TLR4/MyD88/NF-κB signaling within the PVN. To examine this hypothesis, two-kidney-one-clip (2K1C) renovascular hypertensive rats were assigned to two groups: sedentary or exercise training and examined for eight weeks. At the same time, bilateral PVN infusion of vehicle or TAK242, a TLR4 inhibitor, was performed on both groups. As a result, the systolic blood pressure (SBP), renal sympathetic nerve activity (RSNA) and plasma levels of norepinephrine (NE), epinephrine (EPI) were found significantly increased in 2K1C hypertensive rats. These rats also had higher levels of Fra-like activity, NF-κB p65 activity, TLR4, MyD88, IL-1β and TNF-α in the PVN than SHAM rats. Eight weeks of ExT attenuated the RSNA and SBP, repressed the NF-κB p65 activity, and reduced the increase of plasma levels of NE, EPI, and the expression of Fra-like, TLR4, MyD88, IL-1β and TNF-α in the PVN of 2K1C rats. These findings are highly similar to the results in 2K1C rats with bilateral PVN infusions of TLR4 inhibitor (TAK242). This suggests that eight weeks of ExT may decrease blood pressure in hypertensive rats by reducing the PICs activation through TLR4/MyD88/NF-κB signaling within the PVN, and thus delays the progression of 2K1C renovascular hypertension.

Keywords: Hypothalamic paraventricular nucleus, exercise training, Hypertension, Pro-inflammatory cytokines, TLR4

Received: 23 Aug 2019; Accepted: 09 Oct 2019.

Copyright: © 2019 Qi, Yu, Fu, Liu, Kang, Li and Kang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Yu-Ming Kang, Department of Physiology and Pathophysiology, School of Basic Medical College, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China, ykang@mail.xjtu.edu.cn