Abstract 5942: Left Ventricular Hypertrophy Enhances the Expression of Mineralocorticoid Receptor and Epithelial Na Channels in the Brain and Leads to Salt-sensitive Sympathetic Hyperactivation and Left Ventricular Dysfunction
Background: Recently, we demonstrated that left ventricular hypertrophy (LVH) facilitated salt (Na) uptake from plasma to cerebrospinal fluid (CSF) and sensitized sympathetic activity to the increase in CSF Na concentration. However, the mechanisms of the observations remain unknown. We hypothesized that LVH activates mineralocorticoid receptor (MR) and enhances the expression of epithelial Na channels (ENaCs) in the brain.
Methods and Results: We created LVH in mice by aortic banding (AB). Sham-operated mice served as controls. Four weeks after AB, mice were fed either a high-salt (AB-H) or regular-salt (AB-R) diet for additional 4 weeks. AB-H mice demonstrated the severe deterioration of %FS and significant increases in 24-h urinary norepinephrine excretion (U-NE) compared with AB-R mice or Sham mice (%FS: 27±2 versus 37±1 or 45±2 %, respectively, U-NE: 781±57 versus 514±25 or 373±51 ng/day, respectively, n=6 for each, p<0.05). The expression of MR and ENaCs proteins in the brain was significantly greater in AB-R mice than in Sham mice. Furthermore, this enhanced expression of MR and ENaCs were still evident in AB-H mice, despite the high salt loading. Intracerebroventricular (ICV) infusion of eplerenone, a selective MR blocker (for 4 weeks concomitant with high salt loading), prevented salt-induced sympathetic activation and LV dysfunction in AB mice (U-NE: 410±21 versus 781±57 ng/day, %FS: 42±2 versus 27±2 %, n=6 for each, p<0.05 compared with AB-H mice). ICV infusion of benzamil, a selective ENaC blocker, had similar effects. (U-NE: 519±11 versus 781±57 ng/day, %FS: 40±2 versus 27±2 %, n=4 – 6, p<0.05 compared with AB-H mice).
Conclusions: LVH enhances MR and ENaCs expressions in the brain and leads to salt-sensitive sympathetic hyperactivation and LV dysfunction. Blockade of MR or ENaCs antagonizes salt induced adverse effects.