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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2022-09-01
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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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