Mineralocorticoid receptors/epithelial Na + channels in the choroid plexus are involved in hypertensive mechanisms in stroke-prone spontaneously hypertensive rats

Masatsugu Nakano, Yoshitaka Hirooka, Ryuichi Matsukawa, Koji Ito, Kenji Sunagawa

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Increase in cerebrospinal fluid (CSF) Na + concentration (Na +) precedes hypertension and is a key step in the development of salt-induced hypertension. In the choroid plexus (CP), epithelial Na + channels (ENaCs) have an important role in Na + transport from the blood into the CSF. However, it remains unknown whether the mineralocorticoid receptors (MR)/ENaCs pathway in the CP of stroke-prone spontaneously hypertensive rats (SHRSP) is involved in neural mechanisms of hypertension. Therefore, we examined the role of the MR/ENaCs pathway in the CP in the development of hypertension in SHRSP associated with an increase in CSF Na +As a marker of MR activation, serum/glucocorticoid-inducible kinase 1 (Sgk1) expression levels in the CP were measured and found to be greater in SHRSP than in Wistar-Kyoto (WKY) rats. CSF Na + levels were also higher in SHRSP than in WKY rats. In SHRSP, high-salt intake (8%) increased blood pressure and urinary norepinephrine excretion compared with those in animals fed a regular salt diet (0.5%) for 2 weeks. Furthermore, the expression levels of MR, Sgk1 and ENaCs in the CP and the increase in CSF Na + were greater in SHRSP fed a high-salt diet than in those fed a regular salt diet. These alterations were attenuated by intracerebroventricular infusion of eplerenone (10 μg kg-1 per day), except for α-ENaC and β-ENaC. We conclude that activation of the MR/ENaCs pathway in the CP contributes to hypertension via an increase in CSF Na + thereby exaggerating salt-induced hypertension with sympathetic hyperactivation in SHRSP.

Original languageEnglish
Pages (from-to)277-284
Number of pages8
JournalHypertension Research
Volume36
Issue number3
DOIs
Publication statusPublished - Mar 1 2013

Fingerprint

Epithelial Sodium Channels
Mineralocorticoid Receptors
Choroid Plexus
Inbred SHR Rats
Cerebrospinal Fluid
Stroke
Salts
Hypertension
Inbred WKY Rats
Diet
Glucocorticoids
Intraventricular Infusions
Norepinephrine
Blood Pressure

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Mineralocorticoid receptors/epithelial Na + channels in the choroid plexus are involved in hypertensive mechanisms in stroke-prone spontaneously hypertensive rats. / Nakano, Masatsugu; Hirooka, Yoshitaka; Matsukawa, Ryuichi; Ito, Koji; Sunagawa, Kenji.

In: Hypertension Research, Vol. 36, No. 3, 01.03.2013, p. 277-284.

Research output: Contribution to journalArticle

Nakano, Masatsugu ; Hirooka, Yoshitaka ; Matsukawa, Ryuichi ; Ito, Koji ; Sunagawa, Kenji. / Mineralocorticoid receptors/epithelial Na + channels in the choroid plexus are involved in hypertensive mechanisms in stroke-prone spontaneously hypertensive rats. In: Hypertension Research. 2013 ; Vol. 36, No. 3. pp. 277-284.
@article{b20436c0612040e09f4890cd25663f3c,
title = "Mineralocorticoid receptors/epithelial Na + channels in the choroid plexus are involved in hypertensive mechanisms in stroke-prone spontaneously hypertensive rats",
abstract = "Increase in cerebrospinal fluid (CSF) Na + concentration (Na +) precedes hypertension and is a key step in the development of salt-induced hypertension. In the choroid plexus (CP), epithelial Na + channels (ENaCs) have an important role in Na + transport from the blood into the CSF. However, it remains unknown whether the mineralocorticoid receptors (MR)/ENaCs pathway in the CP of stroke-prone spontaneously hypertensive rats (SHRSP) is involved in neural mechanisms of hypertension. Therefore, we examined the role of the MR/ENaCs pathway in the CP in the development of hypertension in SHRSP associated with an increase in CSF Na +As a marker of MR activation, serum/glucocorticoid-inducible kinase 1 (Sgk1) expression levels in the CP were measured and found to be greater in SHRSP than in Wistar-Kyoto (WKY) rats. CSF Na + levels were also higher in SHRSP than in WKY rats. In SHRSP, high-salt intake (8{\%}) increased blood pressure and urinary norepinephrine excretion compared with those in animals fed a regular salt diet (0.5{\%}) for 2 weeks. Furthermore, the expression levels of MR, Sgk1 and ENaCs in the CP and the increase in CSF Na + were greater in SHRSP fed a high-salt diet than in those fed a regular salt diet. These alterations were attenuated by intracerebroventricular infusion of eplerenone (10 μg kg-1 per day), except for α-ENaC and β-ENaC. We conclude that activation of the MR/ENaCs pathway in the CP contributes to hypertension via an increase in CSF Na + thereby exaggerating salt-induced hypertension with sympathetic hyperactivation in SHRSP.",
author = "Masatsugu Nakano and Yoshitaka Hirooka and Ryuichi Matsukawa and Koji Ito and Kenji Sunagawa",
year = "2013",
month = "3",
day = "1",
doi = "10.1038/hr.2012.174",
language = "English",
volume = "36",
pages = "277--284",
journal = "Hypertension Research",
issn = "0916-9636",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Mineralocorticoid receptors/epithelial Na + channels in the choroid plexus are involved in hypertensive mechanisms in stroke-prone spontaneously hypertensive rats

AU - Nakano, Masatsugu

AU - Hirooka, Yoshitaka

AU - Matsukawa, Ryuichi

AU - Ito, Koji

AU - Sunagawa, Kenji

PY - 2013/3/1

Y1 - 2013/3/1

N2 - Increase in cerebrospinal fluid (CSF) Na + concentration (Na +) precedes hypertension and is a key step in the development of salt-induced hypertension. In the choroid plexus (CP), epithelial Na + channels (ENaCs) have an important role in Na + transport from the blood into the CSF. However, it remains unknown whether the mineralocorticoid receptors (MR)/ENaCs pathway in the CP of stroke-prone spontaneously hypertensive rats (SHRSP) is involved in neural mechanisms of hypertension. Therefore, we examined the role of the MR/ENaCs pathway in the CP in the development of hypertension in SHRSP associated with an increase in CSF Na +As a marker of MR activation, serum/glucocorticoid-inducible kinase 1 (Sgk1) expression levels in the CP were measured and found to be greater in SHRSP than in Wistar-Kyoto (WKY) rats. CSF Na + levels were also higher in SHRSP than in WKY rats. In SHRSP, high-salt intake (8%) increased blood pressure and urinary norepinephrine excretion compared with those in animals fed a regular salt diet (0.5%) for 2 weeks. Furthermore, the expression levels of MR, Sgk1 and ENaCs in the CP and the increase in CSF Na + were greater in SHRSP fed a high-salt diet than in those fed a regular salt diet. These alterations were attenuated by intracerebroventricular infusion of eplerenone (10 μg kg-1 per day), except for α-ENaC and β-ENaC. We conclude that activation of the MR/ENaCs pathway in the CP contributes to hypertension via an increase in CSF Na + thereby exaggerating salt-induced hypertension with sympathetic hyperactivation in SHRSP.

AB - Increase in cerebrospinal fluid (CSF) Na + concentration (Na +) precedes hypertension and is a key step in the development of salt-induced hypertension. In the choroid plexus (CP), epithelial Na + channels (ENaCs) have an important role in Na + transport from the blood into the CSF. However, it remains unknown whether the mineralocorticoid receptors (MR)/ENaCs pathway in the CP of stroke-prone spontaneously hypertensive rats (SHRSP) is involved in neural mechanisms of hypertension. Therefore, we examined the role of the MR/ENaCs pathway in the CP in the development of hypertension in SHRSP associated with an increase in CSF Na +As a marker of MR activation, serum/glucocorticoid-inducible kinase 1 (Sgk1) expression levels in the CP were measured and found to be greater in SHRSP than in Wistar-Kyoto (WKY) rats. CSF Na + levels were also higher in SHRSP than in WKY rats. In SHRSP, high-salt intake (8%) increased blood pressure and urinary norepinephrine excretion compared with those in animals fed a regular salt diet (0.5%) for 2 weeks. Furthermore, the expression levels of MR, Sgk1 and ENaCs in the CP and the increase in CSF Na + were greater in SHRSP fed a high-salt diet than in those fed a regular salt diet. These alterations were attenuated by intracerebroventricular infusion of eplerenone (10 μg kg-1 per day), except for α-ENaC and β-ENaC. We conclude that activation of the MR/ENaCs pathway in the CP contributes to hypertension via an increase in CSF Na + thereby exaggerating salt-induced hypertension with sympathetic hyperactivation in SHRSP.

UR - http://www.scopus.com/inward/record.url?scp=84874582849&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84874582849&partnerID=8YFLogxK

U2 - 10.1038/hr.2012.174

DO - 10.1038/hr.2012.174

M3 - Article

C2 - 23096235

AN - SCOPUS:84874582849

VL - 36

SP - 277

EP - 284

JO - Hypertension Research

JF - Hypertension Research

SN - 0916-9636

IS - 3

ER -