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.

• Authors: Masatsugu Nakano, Yoshitaka Hirooka, Ryuichi Matsukawa, Koji Ito, Kenji Sunagawa
• Journal: Hypertension research : official journal of the Japanese Society of Hypertension (Hypertens Res) Vol. 36 Issue 3 Pg. 277-84 (Mar 2013) ISSN: 1348-4214 [Electronic] England
• PMID: 23096235 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Epithelial Sodium Channels
• Immediate-Early Proteins
• Mineralocorticoid Receptor Antagonists
• Receptors, Mineralocorticoid
• Sodium Chloride, Dietary
• Spironolactone
• Eplerenone
• Sodium
• Protein Serine-Threonine Kinases
• serum-glucocorticoid regulated kinase

Topics

• Animals
• Blood Pressure (drug effects, physiology)
• Choroid Plexus (metabolism)
• Disease Models, Animal
• Epithelial Sodium Channels (metabolism)
• Eplerenone
• Hypertension (chemically induced, complications, metabolism)
• Immediate-Early Proteins (metabolism)
• Male
• Mineralocorticoid Receptor Antagonists (pharmacology)
• Protein Serine-Threonine Kinases (metabolism)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Receptors, Mineralocorticoid (drug effects, metabolism)
• Risk Factors
• Signal Transduction (physiology)
• Sodium (blood, cerebrospinal fluid)
• Sodium Chloride, Dietary (adverse effects, pharmacology)
• Spironolactone (analogs & derivatives, pharmacology)
• Stroke (epidemiology, metabolism)