Impact of Selective Renal Afferent Denervation on Oxidative Stress and Vascular Remodeling in Spontaneously Hypertensive Rats

Oxidative stress and sustained sympathetic over-activity contribute to the pathogenesis of hypertension. Catheter-based renal denervation has been used as a strategy for treatment of resistant hypertension, which interrupts both afferent and efferent renal fibers. However, it is unknown whether sele...

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Main Authors: Lu-Lu Wu, Yue Zhang, Xiu-Zhen Li, Xin-Li Du, Ying Gao, Jing-Xiao Wang, Xiao-Li Wang, Qi Chen, Yue-Hua Li, Guo-Qing Zhu, Xiao Tan
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/11/5/1003
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author Lu-Lu Wu
Yue Zhang
Xiu-Zhen Li
Xin-Li Du
Ying Gao
Jing-Xiao Wang
Xiao-Li Wang
Qi Chen
Yue-Hua Li
Guo-Qing Zhu
Xiao Tan
author_facet Lu-Lu Wu
Yue Zhang
Xiu-Zhen Li
Xin-Li Du
Ying Gao
Jing-Xiao Wang
Xiao-Li Wang
Qi Chen
Yue-Hua Li
Guo-Qing Zhu
Xiao Tan
author_sort Lu-Lu Wu
collection DOAJ
description Oxidative stress and sustained sympathetic over-activity contribute to the pathogenesis of hypertension. Catheter-based renal denervation has been used as a strategy for treatment of resistant hypertension, which interrupts both afferent and efferent renal fibers. However, it is unknown whether selective renal afferent denervation (RAD) may play beneficial roles in attenuating oxidative stress and sympathetic activity in hypertension. This study investigated the impact of selective RAD on hypertension and vascular remodeling. Nine-week-old normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were subjected to selective renal afferent denervation (RAD) with 33 mM of capsaicin for 15 min. Treatment with the vehicle of capsaicin was used as a control. The selective denervation was confirmed by the reduced calcitonin gene-related peptide expression and the undamaged renal sympathetic nerve activity response to the stimulation of adipose white tissue. Selective RAD reduced plasma norepinephrine levels, improved heart rate variability (HRV) and attenuated hypertension in SHR.It reduced NADPH oxidase (NOX) expression and activity, and superoxide production in the hypothalamic paraventricular nucleus (PVN), aorta and mesenteric artery of SHR. Moreover, the selective RAD attenuated the vascular remodeling of the aorta and mesenteric artery of SHR. These results indicate that selective removal of renal afferents attenuates sympathetic activity, oxidative stress, vascular remodeling and hypertension in SHR. The attenuated superoxide signaling in the PVN is involved in the attenuation of sympathetic activity in SHR, and the reduced sympathetic activity at least partially contributes to the attenuation of vascular oxidative stress and remodeling in the arteries of hypertensive rats.
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spelling doaj.art-055c9fb464b8497a87abc362a687e8682023-11-23T09:52:58ZengMDPI AGAntioxidants2076-39212022-05-01115100310.3390/antiox11051003Impact of Selective Renal Afferent Denervation on Oxidative Stress and Vascular Remodeling in Spontaneously Hypertensive RatsLu-Lu Wu0Yue Zhang1Xiu-Zhen Li2Xin-Li Du3Ying Gao4Jing-Xiao Wang5Xiao-Li Wang6Qi Chen7Yue-Hua Li8Guo-Qing Zhu9Xiao Tan10Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, and Department of Physiology, Nanjing Medical University, Nanjing 211166, ChinaEmergency Department, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 211166, ChinaEmergency Department, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 211166, ChinaEmergency Department, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 211166, ChinaEmergency Department, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 211166, ChinaKey Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, and Department of Physiology, Nanjing Medical University, Nanjing 211166, ChinaKey Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, and Department of Physiology, Nanjing Medical University, Nanjing 211166, ChinaDepartment of Pathophysiology, Nanjing Medical University, Nanjing 211166, ChinaDepartment of Pathophysiology, Nanjing Medical University, Nanjing 211166, ChinaKey Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, and Department of Physiology, Nanjing Medical University, Nanjing 211166, ChinaEmergency Department, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 211166, ChinaOxidative stress and sustained sympathetic over-activity contribute to the pathogenesis of hypertension. Catheter-based renal denervation has been used as a strategy for treatment of resistant hypertension, which interrupts both afferent and efferent renal fibers. However, it is unknown whether selective renal afferent denervation (RAD) may play beneficial roles in attenuating oxidative stress and sympathetic activity in hypertension. This study investigated the impact of selective RAD on hypertension and vascular remodeling. Nine-week-old normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were subjected to selective renal afferent denervation (RAD) with 33 mM of capsaicin for 15 min. Treatment with the vehicle of capsaicin was used as a control. The selective denervation was confirmed by the reduced calcitonin gene-related peptide expression and the undamaged renal sympathetic nerve activity response to the stimulation of adipose white tissue. Selective RAD reduced plasma norepinephrine levels, improved heart rate variability (HRV) and attenuated hypertension in SHR.It reduced NADPH oxidase (NOX) expression and activity, and superoxide production in the hypothalamic paraventricular nucleus (PVN), aorta and mesenteric artery of SHR. Moreover, the selective RAD attenuated the vascular remodeling of the aorta and mesenteric artery of SHR. These results indicate that selective removal of renal afferents attenuates sympathetic activity, oxidative stress, vascular remodeling and hypertension in SHR. The attenuated superoxide signaling in the PVN is involved in the attenuation of sympathetic activity in SHR, and the reduced sympathetic activity at least partially contributes to the attenuation of vascular oxidative stress and remodeling in the arteries of hypertensive rats.https://www.mdpi.com/2076-3921/11/5/1003oxidative stressrenal afferentshypertensionsympathetic activityvascular remodeling
spellingShingle Lu-Lu Wu
Yue Zhang
Xiu-Zhen Li
Xin-Li Du
Ying Gao
Jing-Xiao Wang
Xiao-Li Wang
Qi Chen
Yue-Hua Li
Guo-Qing Zhu
Xiao Tan
Impact of Selective Renal Afferent Denervation on Oxidative Stress and Vascular Remodeling in Spontaneously Hypertensive Rats
Antioxidants
oxidative stress
renal afferents
hypertension
sympathetic activity
vascular remodeling
title Impact of Selective Renal Afferent Denervation on Oxidative Stress and Vascular Remodeling in Spontaneously Hypertensive Rats
title_full Impact of Selective Renal Afferent Denervation on Oxidative Stress and Vascular Remodeling in Spontaneously Hypertensive Rats
title_fullStr Impact of Selective Renal Afferent Denervation on Oxidative Stress and Vascular Remodeling in Spontaneously Hypertensive Rats
title_full_unstemmed Impact of Selective Renal Afferent Denervation on Oxidative Stress and Vascular Remodeling in Spontaneously Hypertensive Rats
title_short Impact of Selective Renal Afferent Denervation on Oxidative Stress and Vascular Remodeling in Spontaneously Hypertensive Rats
title_sort impact of selective renal afferent denervation on oxidative stress and vascular remodeling in spontaneously hypertensive rats
topic oxidative stress
renal afferents
hypertension
sympathetic activity
vascular remodeling
url https://www.mdpi.com/2076-3921/11/5/1003
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