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.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Nakano
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hirooka
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Matsukawa
authors.forename: Koji
authors.initials: K
authors.lastname: Ito
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002831:Choroid Plexus / Q000378:metabolism*; D004195:Disease Models, Animal; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D000077545:Eplerenone; D006973:Hypertension / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000378:metabolism; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000378:metabolism*; D012307:Risk Factors; D015398:Signal Transduction / Q000502:physiology; D012964:Sodium / Q000097:blood / Q000134:cerebrospinal fluid; D017673:Sodium Chloride, Dietary / Q000009:adverse effects / Q000494:pharmacology; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D020521:Stroke / Q000453:epidemiology* / Q000378:metabolism*; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D053503:Epithelial Sodium Channels; D000077545:Eplerenone; D017874:Immediate-Early Proteins; D000451:Mineralocorticoid Receptor Antagonists; D017346:Protein Serine-Threonine Kinases; D018161:Receptors, Mineralocorticoid; D012964:Sodium; D017673:Sodium Chloride, Dietary; D013148:Spironolactone; D000099184:Serum-Glucocorticoid Regulated Kinases