Renal denervation has blood pressure-independent protective effects on kidney and heart in a rat model of chronic kidney disease

Masahiro Eriguchi, Kazuhiko Tsuruya, Naoki Haruyama, Shunsuke Yamada, Shigeru Tanaka, Takaichi Suehiro, Hideko Noguchi, Kosuke Masutani, Kumiko Torisu, Takanari Kitazono

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

We elucidate The underlying mechanisms of bidirectional cardiorenal interaction, focusing on The sympathetic nerve driving disruption of The local renin-angiotensin system (RAS). A rat model of N ω-nitro-L-arginine methyl ester (L-NAME; a nitric oxide synthase inhibitor) administration was used to induce damage in The heart and kidney, similar to cardiorenal syndrome. L-NAME induced sympathetic nerve-RAS overactivity and cardiorenal injury accompanied by local RAS elevations. These were suppressed by bilateral renal denervation, but not by hydralazine treatment, despite The blood pressure being kept The same between The two groups. Although L-NAME induced angiotensinogen (AGT) protein augmentation in both organs, AGT mRNA decreased in The kidney and increased in The heart in a contradictory manner. Immunostaining for AGT suggested that renal denervation suppressed AGT onsite generation from activated resident macrophages of The heart and circulating AGT excretion from glomeruli of The kidney. We also examined rats treated with L-NAME plus unilateral denervation to confirm direct sympathetic regulation of intrarenal RAS. The levels of urinary AGT and renal angiotensin II content and The degrees of renal injury from denervated kidneys were less than those from contralateral innervated kidneys within The same rats. Thus, renal denervation has blood pressure-independent beneficial effects associated with local RAS inhibition.

Original languageEnglish
Pages (from-to)116-127
Number of pages12
JournalKidney International
Volume87
Issue number1
DOIs
Publication statusPublished - Jan 3 2015

Fingerprint

Denervation
Chronic Renal Insufficiency
Angiotensinogen
Blood Pressure
Kidney
Renin-Angiotensin System
NG-Nitroarginine Methyl Ester
Cardio-Renal Syndrome
Kidney Glomerulus
Hydralazine
Wounds and Injuries
Nitric Oxide Synthase
Angiotensin II
Macrophages
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Renal denervation has blood pressure-independent protective effects on kidney and heart in a rat model of chronic kidney disease. / Eriguchi, Masahiro; Tsuruya, Kazuhiko; Haruyama, Naoki; Yamada, Shunsuke; Tanaka, Shigeru; Suehiro, Takaichi; Noguchi, Hideko; Masutani, Kosuke; Torisu, Kumiko; Kitazono, Takanari.

In: Kidney International, Vol. 87, No. 1, 03.01.2015, p. 116-127.

Research output: Contribution to journalArticle

Eriguchi, Masahiro ; Tsuruya, Kazuhiko ; Haruyama, Naoki ; Yamada, Shunsuke ; Tanaka, Shigeru ; Suehiro, Takaichi ; Noguchi, Hideko ; Masutani, Kosuke ; Torisu, Kumiko ; Kitazono, Takanari. / Renal denervation has blood pressure-independent protective effects on kidney and heart in a rat model of chronic kidney disease. In: Kidney International. 2015 ; Vol. 87, No. 1. pp. 116-127.
@article{79d9d00e03094f628ab1b992a12728ea,
title = "Renal denervation has blood pressure-independent protective effects on kidney and heart in a rat model of chronic kidney disease",
abstract = "We elucidate The underlying mechanisms of bidirectional cardiorenal interaction, focusing on The sympathetic nerve driving disruption of The local renin-angiotensin system (RAS). A rat model of N ω-nitro-L-arginine methyl ester (L-NAME; a nitric oxide synthase inhibitor) administration was used to induce damage in The heart and kidney, similar to cardiorenal syndrome. L-NAME induced sympathetic nerve-RAS overactivity and cardiorenal injury accompanied by local RAS elevations. These were suppressed by bilateral renal denervation, but not by hydralazine treatment, despite The blood pressure being kept The same between The two groups. Although L-NAME induced angiotensinogen (AGT) protein augmentation in both organs, AGT mRNA decreased in The kidney and increased in The heart in a contradictory manner. Immunostaining for AGT suggested that renal denervation suppressed AGT onsite generation from activated resident macrophages of The heart and circulating AGT excretion from glomeruli of The kidney. We also examined rats treated with L-NAME plus unilateral denervation to confirm direct sympathetic regulation of intrarenal RAS. The levels of urinary AGT and renal angiotensin II content and The degrees of renal injury from denervated kidneys were less than those from contralateral innervated kidneys within The same rats. Thus, renal denervation has blood pressure-independent beneficial effects associated with local RAS inhibition.",
author = "Masahiro Eriguchi and Kazuhiko Tsuruya and Naoki Haruyama and Shunsuke Yamada and Shigeru Tanaka and Takaichi Suehiro and Hideko Noguchi and Kosuke Masutani and Kumiko Torisu and Takanari Kitazono",
year = "2015",
month = "1",
day = "3",
doi = "10.1038/ki.2014.220",
language = "English",
volume = "87",
pages = "116--127",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Renal denervation has blood pressure-independent protective effects on kidney and heart in a rat model of chronic kidney disease

AU - Eriguchi, Masahiro

AU - Tsuruya, Kazuhiko

AU - Haruyama, Naoki

AU - Yamada, Shunsuke

AU - Tanaka, Shigeru

AU - Suehiro, Takaichi

AU - Noguchi, Hideko

AU - Masutani, Kosuke

AU - Torisu, Kumiko

AU - Kitazono, Takanari

PY - 2015/1/3

Y1 - 2015/1/3

N2 - We elucidate The underlying mechanisms of bidirectional cardiorenal interaction, focusing on The sympathetic nerve driving disruption of The local renin-angiotensin system (RAS). A rat model of N ω-nitro-L-arginine methyl ester (L-NAME; a nitric oxide synthase inhibitor) administration was used to induce damage in The heart and kidney, similar to cardiorenal syndrome. L-NAME induced sympathetic nerve-RAS overactivity and cardiorenal injury accompanied by local RAS elevations. These were suppressed by bilateral renal denervation, but not by hydralazine treatment, despite The blood pressure being kept The same between The two groups. Although L-NAME induced angiotensinogen (AGT) protein augmentation in both organs, AGT mRNA decreased in The kidney and increased in The heart in a contradictory manner. Immunostaining for AGT suggested that renal denervation suppressed AGT onsite generation from activated resident macrophages of The heart and circulating AGT excretion from glomeruli of The kidney. We also examined rats treated with L-NAME plus unilateral denervation to confirm direct sympathetic regulation of intrarenal RAS. The levels of urinary AGT and renal angiotensin II content and The degrees of renal injury from denervated kidneys were less than those from contralateral innervated kidneys within The same rats. Thus, renal denervation has blood pressure-independent beneficial effects associated with local RAS inhibition.

AB - We elucidate The underlying mechanisms of bidirectional cardiorenal interaction, focusing on The sympathetic nerve driving disruption of The local renin-angiotensin system (RAS). A rat model of N ω-nitro-L-arginine methyl ester (L-NAME; a nitric oxide synthase inhibitor) administration was used to induce damage in The heart and kidney, similar to cardiorenal syndrome. L-NAME induced sympathetic nerve-RAS overactivity and cardiorenal injury accompanied by local RAS elevations. These were suppressed by bilateral renal denervation, but not by hydralazine treatment, despite The blood pressure being kept The same between The two groups. Although L-NAME induced angiotensinogen (AGT) protein augmentation in both organs, AGT mRNA decreased in The kidney and increased in The heart in a contradictory manner. Immunostaining for AGT suggested that renal denervation suppressed AGT onsite generation from activated resident macrophages of The heart and circulating AGT excretion from glomeruli of The kidney. We also examined rats treated with L-NAME plus unilateral denervation to confirm direct sympathetic regulation of intrarenal RAS. The levels of urinary AGT and renal angiotensin II content and The degrees of renal injury from denervated kidneys were less than those from contralateral innervated kidneys within The same rats. Thus, renal denervation has blood pressure-independent beneficial effects associated with local RAS inhibition.

UR - http://www.scopus.com/inward/record.url?scp=84920263557&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84920263557&partnerID=8YFLogxK

U2 - 10.1038/ki.2014.220

DO - 10.1038/ki.2014.220

M3 - Article

C2 - 24940798

AN - SCOPUS:84920263557

VL - 87

SP - 116

EP - 127

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 1

ER -