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

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    31 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 2013

    All Science Journal Classification (ASJC) codes

    • Internal Medicine
    • Physiology
    • Cardiology and Cardiovascular Medicine

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