Abstract 1622: High salt Intake Superimposed On Left Ventricular Hypertrophy Activates Brain Enac And Leads To Sympathetic Hyperactivation And Ventricular Dysfunction

Background: High-salt intake often predisposes patients with left ventricular hypertrophy (LVH) to congestive heart failure. We hypothesized that high-salt intake superimposed on LVH activates brain epithelial Na channels (ENaC) and leads to sympathetic hyperactivation and LV dysfunction. Methods and Results: We used ICR mice and applied aortic banding (AB) to create LVH. Sham-operated mice served as control. Four weeks after AB, 24-h urinary norepinephrine excretion (U-NE) tended to increase rather than that in control (481±46 vs 354±42, n=10, p=0.09). AB hypertrophied LV wall thickness (WT) (2.2±0.6 vs 1.8±0.6 mm, n=8, p<0.05) without changing fractional shortening (%FS). We then fed the AB mice a high salt (8%) (AB-H) or regular salt (AB-R) diet for additional 4 weeks. AB-H depressed LV function (%FS: 27±2 vs 37±1%, n=8, p<0.05) and hypertrophied LVWT more than those in AB-R (WT: 2.8±0.5 vs 2.5±0.3 mm, n=8, p<0.05). U-NE was higher in AB-H than in AB-R (758±86 vs 459±35 ng/day, n=10, p<0.05). To examine the role of brain ENaC, we intracerebroventriculary (ICV) infused ENaC blocker (benzamil, 0.11μg/hr by osmotic pump) in AB-H for 4weeks. ENaC blocker decreased U-NE (567±35 vs 758±86 ng/day, n=10, p<0.05) and improved depressed LV function (%FS: 39±1 vs 28±3 %, n=10, p<0.05). To confirm the role of central Na in sympathetic hyperactivation and LV dysfunction, we administered, in AB with regular salt diet, high-Na (0.2 M) cerebrospinal fluid ICV (Na-ICV) (0.25μl/hr) for 2 weeks. Na-ICV significantly increased U-NE and deteriorates LV function (U-NE:987±103 ng/day, %FS: 31±1 %n=6) Conclusions: These results suggested that high-salt intake in the presence of LVH activates brain ENaC and leads to sympathetic hyperactivation and LV dysfunction.