Renal denervation enhances GABA-ergic input into the PVN leading to blood pressure lowering in chronic kidney disease

Masaaki Nishihara, Ko Takesue, Yoshitaka Hirooka

研究成果: ジャーナルへの寄稿評論記事

6 引用 (Scopus)

抄録

Objective Sympathoexcitation plays an important role in the pathogenesis of hypertension in patients with chronic kidney disease (CKD). The paraventricular nucleus of the hypothalamus (PVN) in the brain controls sympathetic outflow through γ-amino butyric acid (GABA)-ergic mechanisms. Renal denervation (RDN) exerts a long-term antihypertensive effect in hypertension with CKD; however, the effects of RDN on sympathetic nerve activity and GABA-ergic modulation in the PVN are not clear. We aimed to elucidate whether RDN modulates sympathetic outflow through GABA-ergic mechanisms in the PVN in hypertensive mice with CKD. Methods and results In 5/6-nephrectomized male Institute of Cancer Research mice (Nx) at 4 weeks after nephrectomy, systolic blood pressure (SBP) was significantly increased, accompanied by sympathoexcitation. The Nx-mice underwent RDN or sham operation, and the mice were divided into three groups (Control, Nx-Sham, and Nx-RDN). At 2 weeks after RDN, SBP was significantly decreased and urinary sodium excretion was increased in Nx-RDN compared with Nx-Sham. Urinary norepinephrine excretion (uNE) levels did not differ significantly between Nx-RDN and Nx-Sham. At 6 weeks after RDN, SBP continued to decrease and uNE levels also decreased in Nx-RDN compared with Nx-Sham. Bicuculline microinjection into the PVN increased mean arterial pressure and lumbar sympathetic nerve activity in all groups. The pressor responses and change in lumbar sympathetic nerve activity were significantly attenuated in Nx-Sham, but were enhanced in Nx-RDN at 6 weeks after RDN. Conclusions The findings from the present study indicate that RDN has a prolonged antihypertensive effect and, at least in the late phase, decreases sympathetic nerve activity in association with enhanced GABA-ergic input into the PVN in mice with CKD.

元の言語英語
ページ(範囲)88-97
ページ数10
ジャーナルAutonomic Neuroscience: Basic and Clinical
204
DOI
出版物ステータス出版済み - 5 1 2017

Fingerprint

Paraventricular Hypothalamic Nucleus
Denervation
Chronic Renal Insufficiency
gamma-Aminobutyric Acid
Hypothalamus
Blood Pressure
Kidney
Sympathectomy
Antihypertensive Agents
Norepinephrine
Hypertension
Butyric Acid
Bicuculline
Microinjections
Nephrectomy
Arterial Pressure
Sodium

All Science Journal Classification (ASJC) codes

  • Endocrine and Autonomic Systems
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

これを引用

Renal denervation enhances GABA-ergic input into the PVN leading to blood pressure lowering in chronic kidney disease. / Nishihara, Masaaki; Takesue, Ko; Hirooka, Yoshitaka.

:: Autonomic Neuroscience: Basic and Clinical, 巻 204, 01.05.2017, p. 88-97.

研究成果: ジャーナルへの寄稿評論記事

@article{d92dfe413e80416d86cf5f122b077551,
title = "Renal denervation enhances GABA-ergic input into the PVN leading to blood pressure lowering in chronic kidney disease",
abstract = "Objective Sympathoexcitation plays an important role in the pathogenesis of hypertension in patients with chronic kidney disease (CKD). The paraventricular nucleus of the hypothalamus (PVN) in the brain controls sympathetic outflow through γ-amino butyric acid (GABA)-ergic mechanisms. Renal denervation (RDN) exerts a long-term antihypertensive effect in hypertension with CKD; however, the effects of RDN on sympathetic nerve activity and GABA-ergic modulation in the PVN are not clear. We aimed to elucidate whether RDN modulates sympathetic outflow through GABA-ergic mechanisms in the PVN in hypertensive mice with CKD. Methods and results In 5/6-nephrectomized male Institute of Cancer Research mice (Nx) at 4 weeks after nephrectomy, systolic blood pressure (SBP) was significantly increased, accompanied by sympathoexcitation. The Nx-mice underwent RDN or sham operation, and the mice were divided into three groups (Control, Nx-Sham, and Nx-RDN). At 2 weeks after RDN, SBP was significantly decreased and urinary sodium excretion was increased in Nx-RDN compared with Nx-Sham. Urinary norepinephrine excretion (uNE) levels did not differ significantly between Nx-RDN and Nx-Sham. At 6 weeks after RDN, SBP continued to decrease and uNE levels also decreased in Nx-RDN compared with Nx-Sham. Bicuculline microinjection into the PVN increased mean arterial pressure and lumbar sympathetic nerve activity in all groups. The pressor responses and change in lumbar sympathetic nerve activity were significantly attenuated in Nx-Sham, but were enhanced in Nx-RDN at 6 weeks after RDN. Conclusions The findings from the present study indicate that RDN has a prolonged antihypertensive effect and, at least in the late phase, decreases sympathetic nerve activity in association with enhanced GABA-ergic input into the PVN in mice with CKD.",
author = "Masaaki Nishihara and Ko Takesue and Yoshitaka Hirooka",
year = "2017",
month = "5",
day = "1",
doi = "10.1016/j.autneu.2016.09.018",
language = "English",
volume = "204",
pages = "88--97",
journal = "Autonomic Neuroscience: Basic and Clinical",
issn = "1566-0702",
publisher = "Elsevier",

}

TY - JOUR

T1 - Renal denervation enhances GABA-ergic input into the PVN leading to blood pressure lowering in chronic kidney disease

AU - Nishihara, Masaaki

AU - Takesue, Ko

AU - Hirooka, Yoshitaka

PY - 2017/5/1

Y1 - 2017/5/1

N2 - Objective Sympathoexcitation plays an important role in the pathogenesis of hypertension in patients with chronic kidney disease (CKD). The paraventricular nucleus of the hypothalamus (PVN) in the brain controls sympathetic outflow through γ-amino butyric acid (GABA)-ergic mechanisms. Renal denervation (RDN) exerts a long-term antihypertensive effect in hypertension with CKD; however, the effects of RDN on sympathetic nerve activity and GABA-ergic modulation in the PVN are not clear. We aimed to elucidate whether RDN modulates sympathetic outflow through GABA-ergic mechanisms in the PVN in hypertensive mice with CKD. Methods and results In 5/6-nephrectomized male Institute of Cancer Research mice (Nx) at 4 weeks after nephrectomy, systolic blood pressure (SBP) was significantly increased, accompanied by sympathoexcitation. The Nx-mice underwent RDN or sham operation, and the mice were divided into three groups (Control, Nx-Sham, and Nx-RDN). At 2 weeks after RDN, SBP was significantly decreased and urinary sodium excretion was increased in Nx-RDN compared with Nx-Sham. Urinary norepinephrine excretion (uNE) levels did not differ significantly between Nx-RDN and Nx-Sham. At 6 weeks after RDN, SBP continued to decrease and uNE levels also decreased in Nx-RDN compared with Nx-Sham. Bicuculline microinjection into the PVN increased mean arterial pressure and lumbar sympathetic nerve activity in all groups. The pressor responses and change in lumbar sympathetic nerve activity were significantly attenuated in Nx-Sham, but were enhanced in Nx-RDN at 6 weeks after RDN. Conclusions The findings from the present study indicate that RDN has a prolonged antihypertensive effect and, at least in the late phase, decreases sympathetic nerve activity in association with enhanced GABA-ergic input into the PVN in mice with CKD.

AB - Objective Sympathoexcitation plays an important role in the pathogenesis of hypertension in patients with chronic kidney disease (CKD). The paraventricular nucleus of the hypothalamus (PVN) in the brain controls sympathetic outflow through γ-amino butyric acid (GABA)-ergic mechanisms. Renal denervation (RDN) exerts a long-term antihypertensive effect in hypertension with CKD; however, the effects of RDN on sympathetic nerve activity and GABA-ergic modulation in the PVN are not clear. We aimed to elucidate whether RDN modulates sympathetic outflow through GABA-ergic mechanisms in the PVN in hypertensive mice with CKD. Methods and results In 5/6-nephrectomized male Institute of Cancer Research mice (Nx) at 4 weeks after nephrectomy, systolic blood pressure (SBP) was significantly increased, accompanied by sympathoexcitation. The Nx-mice underwent RDN or sham operation, and the mice were divided into three groups (Control, Nx-Sham, and Nx-RDN). At 2 weeks after RDN, SBP was significantly decreased and urinary sodium excretion was increased in Nx-RDN compared with Nx-Sham. Urinary norepinephrine excretion (uNE) levels did not differ significantly between Nx-RDN and Nx-Sham. At 6 weeks after RDN, SBP continued to decrease and uNE levels also decreased in Nx-RDN compared with Nx-Sham. Bicuculline microinjection into the PVN increased mean arterial pressure and lumbar sympathetic nerve activity in all groups. The pressor responses and change in lumbar sympathetic nerve activity were significantly attenuated in Nx-Sham, but were enhanced in Nx-RDN at 6 weeks after RDN. Conclusions The findings from the present study indicate that RDN has a prolonged antihypertensive effect and, at least in the late phase, decreases sympathetic nerve activity in association with enhanced GABA-ergic input into the PVN in mice with CKD.

UR - http://www.scopus.com/inward/record.url?scp=84992184200&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84992184200&partnerID=8YFLogxK

U2 - 10.1016/j.autneu.2016.09.018

DO - 10.1016/j.autneu.2016.09.018

M3 - Review article

C2 - 27729205

AN - SCOPUS:84992184200

VL - 204

SP - 88

EP - 97

JO - Autonomic Neuroscience: Basic and Clinical

JF - Autonomic Neuroscience: Basic and Clinical

SN - 1566-0702

ER -