Abstract 17099: Mineralocorticoid Receptors (MR)/Epithelial Na Channels (ENaCs) Pathway Activation in Choroid Plexus Exaggerates Salt-Induced Hypertension with Sympathoexcitation in Stoke-Prone Spontaneously Hypertensive Rats
Background: High salt intake increases blood pressure via sympathoexcitation in salt-sensitive rats. An increase in cerebrospinal fluid Na+ concentration (CSF[Na+]) is suggested to be responsible for salt-sensitive sympathoexcitation. Recently, the increase in CSF[Na+] was reported to enhance brain aldosterone synthesis and mineralocorticoid receptors (MR). Choroid plexus (CP) plays a major role in CSF production, including sodium transport from the blood to the CSF. Therefore, we hypothesized that activation of MR/epithelial Na channels (ENaCs) plays a role in Na+ handling in CP thereby increasing CSF[Na+] and enhanced central sympathetic outflow. Therefore, we aimed to investigate whether activation of MR/ENaCs pathway in CP is responsible for sympathoexcitation in SHRSP associated with salt intake.
Methods and Results: We used 12 weeks old SHRSP and Wistar-Kyoto (WKY) rats. Rats were fed a high-salt diet (HS) (8%) or regular-salt diet (RS) (0.5%) for 2 weeks. In SHRSP, HS intake increased systolic blood pressure (SBP) and urinary norepinephrine excretion (uNE) as a marker of sympathoexcitation compared with those with RS (2 weeks after ΔSBP 41.7 ± 3.2 mmHg, ΔuNE 0.24 ± 0.07 μ g/day, n=5 for each, P<0.05). The increase in CSF[Na+] was also greater in SHRSP fed HS than in RS (2 weeks after ΔCSF[Na+]=5.57 ± 0.72 mM, n=10 for each, P<0.05). Serum glucocorticoid inducible kinase 1 (Sgk1), as a marker of activation of MR, and ENaCs expression in CP was significantly greater in SHRSP fed with HS than in SHRSP fed RS. In SHRSP, intracerebroventricular infusion of MR blocker eplerenone (10μ g/kg/day) with HS for 2 weeks attenuated increases in SBP and uNE. Eplerenone attenuated enhanced CSF[Na+] in SHRSP fed HS (157.8 ± 0.92 vs. 161.0 ± 0.73 mM, n=10 for each, P<0.05). Eplerenone also attenuated the enhanced expression in Sgk1 and γ-ENaC in CP in SHRSP. In WKY rats, HS did not cause these alterations observed in SHRSP.
Conclusion: MR/ENaCs pathway activation in CP contributes to the increase in CSF[Na+], thereby exaggerates salt-induced hypertension with sympathoexcitation in SHRSP.
- © 2012 by American Heart Association, Inc.