Exercise Training Attenuates Hypertension via Suppressing ROS/MAPK/NF-κB/AT-1R Pathway in the Hypothalamic Paraventricular Nucleus

Background: Aerobic exercise training (ExT) is beneficial for hypertension, however, its central mechanisms in improving hypertension remain unclear. Since the importance of the up-regulation of angiotensin II type 1 receptor (AT-1R) in the paraventricular nucleus (PVN) of the hypothalamic in sympat...

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Main Authors: Jie Qi, Rui-Juan Li, Li-Yan Fu, Kai-Li Liu, Jin-An Qiao, Yu Yang, Xiao-Jing Yu, Jia-Yue Yu, Ying Li, Hong Tan, Yu-Ming Kang
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/14/19/3968
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author Jie Qi
Rui-Juan Li
Li-Yan Fu
Kai-Li Liu
Jin-An Qiao
Yu Yang
Xiao-Jing Yu
Jia-Yue Yu
Ying Li
Hong Tan
Yu-Ming Kang
author_facet Jie Qi
Rui-Juan Li
Li-Yan Fu
Kai-Li Liu
Jin-An Qiao
Yu Yang
Xiao-Jing Yu
Jia-Yue Yu
Ying Li
Hong Tan
Yu-Ming Kang
author_sort Jie Qi
collection DOAJ
description Background: Aerobic exercise training (ExT) is beneficial for hypertension, however, its central mechanisms in improving hypertension remain unclear. Since the importance of the up-regulation of angiotensin II type 1 receptor (AT-1R) in the paraventricular nucleus (PVN) of the hypothalamic in sympathoexcitation and hypertension has been shown, we testified the hypothesis that aerobic ExT decreases blood pressure in hypertensive rats by down-regulating the AT-1R through reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK)/nuclear factors κB (NF-κB) pathway within the PVN. Methods: Forty-eight male Sprague-Dawley (SD) rats were assigned to the following groups: sham operation (SHAM) + kept sedentary (Sed), SHAM + exercise training (ExT), two kidney-one clamp (2K1C) + Sed, and 2K1C + ExT groups. Results: The 2K1C + Sed hypertensive rats showed higher systolic blood pressure (SBP), upregulated ROS, phosphorylated (p-) p44/42 MAPK, p-p38 MAPK, NF-κB p65 activity, and AT-1R expression in the PVN, and increased circulating norepinephrine (NE) than those of SHAM rats. After eight weeks of aerobic ExT, the 2K1C + ExT hypertensive rats showed attenuated NE and SBP levels, suppressed NF-κB p65 activity, and reduced expression of ROS, p-p44/42 MAPK, p-p38 MAPK, and AT-1R in the PVN, relatively to the 2K1C + Sed group. Conclusions: These data are suggestive of beneficial effects of aerobic ExT in decreasing SBP in hypertensive rats, via down-regulating the ROS/MAPK/NF-κB pathway that targets AT-1R in the PVN, and eventually ameliorating 2K1C-induced hypertension.
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spelling doaj.art-7b2aad652e3a4a4b863b30cf350ca0ab2023-11-23T21:23:19ZengMDPI AGNutrients2072-66432022-09-011419396810.3390/nu14193968Exercise Training Attenuates Hypertension via Suppressing ROS/MAPK/NF-κB/AT-1R Pathway in the Hypothalamic Paraventricular NucleusJie Qi0Rui-Juan Li1Li-Yan Fu2Kai-Li Liu3Jin-An Qiao4Yu Yang5Xiao-Jing Yu6Jia-Yue Yu7Ying Li8Hong Tan9Yu-Ming Kang10Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Infectious Diseases, The Second Affiliated Hospital, Air Force Military Medical University, Xi’an 710038, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an Jiaotong University, Xi’an 710061, ChinaInstitute of Pediatric Diseases, Xi’an Children’s Hospital, Xi’an 710002, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an Jiaotong University, Xi’an 710061, ChinaCollege of Life Sciences, Northwest University, Xi’an 710069, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an Jiaotong University, Xi’an 710061, ChinaBackground: Aerobic exercise training (ExT) is beneficial for hypertension, however, its central mechanisms in improving hypertension remain unclear. Since the importance of the up-regulation of angiotensin II type 1 receptor (AT-1R) in the paraventricular nucleus (PVN) of the hypothalamic in sympathoexcitation and hypertension has been shown, we testified the hypothesis that aerobic ExT decreases blood pressure in hypertensive rats by down-regulating the AT-1R through reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK)/nuclear factors κB (NF-κB) pathway within the PVN. Methods: Forty-eight male Sprague-Dawley (SD) rats were assigned to the following groups: sham operation (SHAM) + kept sedentary (Sed), SHAM + exercise training (ExT), two kidney-one clamp (2K1C) + Sed, and 2K1C + ExT groups. Results: The 2K1C + Sed hypertensive rats showed higher systolic blood pressure (SBP), upregulated ROS, phosphorylated (p-) p44/42 MAPK, p-p38 MAPK, NF-κB p65 activity, and AT-1R expression in the PVN, and increased circulating norepinephrine (NE) than those of SHAM rats. After eight weeks of aerobic ExT, the 2K1C + ExT hypertensive rats showed attenuated NE and SBP levels, suppressed NF-κB p65 activity, and reduced expression of ROS, p-p44/42 MAPK, p-p38 MAPK, and AT-1R in the PVN, relatively to the 2K1C + Sed group. Conclusions: These data are suggestive of beneficial effects of aerobic ExT in decreasing SBP in hypertensive rats, via down-regulating the ROS/MAPK/NF-κB pathway that targets AT-1R in the PVN, and eventually ameliorating 2K1C-induced hypertension.https://www.mdpi.com/2072-6643/14/19/3968exercise trainingparaventricular nucleushypertensionangiotensin II type 1 receptorMAPK
spellingShingle Jie Qi
Rui-Juan Li
Li-Yan Fu
Kai-Li Liu
Jin-An Qiao
Yu Yang
Xiao-Jing Yu
Jia-Yue Yu
Ying Li
Hong Tan
Yu-Ming Kang
Exercise Training Attenuates Hypertension via Suppressing ROS/MAPK/NF-κB/AT-1R Pathway in the Hypothalamic Paraventricular Nucleus
Nutrients
exercise training
paraventricular nucleus
hypertension
angiotensin II type 1 receptor
MAPK
title Exercise Training Attenuates Hypertension via Suppressing ROS/MAPK/NF-κB/AT-1R Pathway in the Hypothalamic Paraventricular Nucleus
title_full Exercise Training Attenuates Hypertension via Suppressing ROS/MAPK/NF-κB/AT-1R Pathway in the Hypothalamic Paraventricular Nucleus
title_fullStr Exercise Training Attenuates Hypertension via Suppressing ROS/MAPK/NF-κB/AT-1R Pathway in the Hypothalamic Paraventricular Nucleus
title_full_unstemmed Exercise Training Attenuates Hypertension via Suppressing ROS/MAPK/NF-κB/AT-1R Pathway in the Hypothalamic Paraventricular Nucleus
title_short Exercise Training Attenuates Hypertension via Suppressing ROS/MAPK/NF-κB/AT-1R Pathway in the Hypothalamic Paraventricular Nucleus
title_sort exercise training attenuates hypertension via suppressing ros mapk nf κb at 1r pathway in the hypothalamic paraventricular nucleus
topic exercise training
paraventricular nucleus
hypertension
angiotensin II type 1 receptor
MAPK
url https://www.mdpi.com/2072-6643/14/19/3968
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