Mineralocorticoid Receptors Activation in Choroid Plexus and PVN Exaggerates Salt‐Induced Development of Hypertension in Stroke‐Prone Spontaneously Hypertensive Rats

Abstract

BackgroundIn salt sensitive models, the increases in cerebrospinal fluid Na+ concentration (CSF [Na]) derived from choroid plexus (CP) play a pivotal role in high salt (HS) induced hypertension. Mineralocorticoid receptors (MR) contribute to Na+ handling. Therefore, we investigated whether MR in CP and paraventricular nucleus of hypothalamus (PVN) exaggerates salt‐induced development of hypertension in stroke‐prone spontaneously hypertensive rats (SHRSP).Methods and ResultsSerum glucocorticoid inducible kinase 1 (sgk1) expression levels in CP and PVN were greater in SHRSP than those in Wistar‐Kyoto (WKY) rats (N=6, P<0.05) associated with increases in CSF[Na] (155.6 ± 0.81 vs. 152.8 ± 0.49 mM, P<0.01). The depressor response to intracerebroventricular (ICV) infusion of MR blocker, eplerenone (10 ng) was greater in SHRSP than in WKY (Δarterial pressure (AP) −25.2 ± 1.4 vs. −8.2 ± 1.4 mmHg, N=5, P<0.001). In SHRSP, HS intake (8%) increased AP and urinary norepinephrine excretion (uNE) compared with those by regular salt diet (2 weeks after ΔAP 41.7 ± 3.2 mmHg, ΔuNE 0.24 ± 0.07 μg/day, N=5, P<0.05) associated with increases in MR and sgk1 expression in CP and PVN. These alterations were attenuated by ICV infusion of eplerenone (10 μg/kg/day).ConclusionMR activation in CP might contribute to increases in CSF[Na], thereby exaggerates salt‐induced development of hypertension via MR activation in PVN in SHRSP.