Abstract 037: Renal Denervation Reduces Salt Preference In Female Spontaneously Hypertensive Rats

Reducing salt intake is a cost-effective way to reduce non-communicable disease. Despite this, Americans consume ~3.4g of sodium daily, 1g more than the AHA’s recommended maximum. Since dietary sodium is not deficient in modern society, the excessive levels of intake are driven, in part, by salt preference, the consumption of sodium without physiological need. Population studies have shown that increased salt preference is associated with an increased risk of cardiovascular and chronic kidney diseases. We have shown that afferent renal denervation (ARDN) reduces salt intake in DOCA-salt rats. In this study, we tested the hypothesis that ARDN would reduce salt intake in spontaneously hypertensive rats (SHR), a model of increased salt preference. Male (M) and female (F) SHR aged 11-12 weeks were studied. ARDN was performed using the periaxonal application of 33mM capsaicin (n=6M, 11F). In sham rats (n=5M, 11F) renal arteries were isolated but not treated. Total renal denervation (TRDN, n=3F) was performed by manually destroying nerves, followed by the application of 10% phenol. In two bottle preference tests, rats had ad libitum access to both deionized water and 1.8% NaCl. In food preference tests, rats had ad libitum access to both low (0.025% NaCl) and high (2% NaCl) salt diets (n=3F, sham and ARDN). Fluid and food intake were recorded daily. Over 3-weeks, female SHR drank significantly more 1.8% NaCl than male SHR (P=0.012). ARDN significantly reduced 1.8% NaCl intake in female but not male SHR (F P=0.001, M P=0.318 vs sham). Because TRDN is FDA approved and clinically relevant, we examined its effect on 1.8% NaCl intake in female SHR. TRDN significantly reduced saline intake (P<0.001 vs sham). Neither ARDN nor TRDN reduced water intake (F P=0.55, M P=0.843, comparing groups). To increase the translatability of our results, we examined the effect of ARDN on the consumption of a high-salt diet in female SHR. Over 7 days, ARDN significantly reduced the consumption of 2% NaCl (P=0.027) but had no effect on the consumption of 0.025% NaCl (P=0.895). Female SHR have a higher salt preference than male SHR. ARDN reduced 1.8% NaCl intake in female but not male SHR, suggesting that elevated afferent renal nerve activity drives the increased salt preference in female SHR. Notably, in female SHR ARDN reduced salt intake in both liquid and dietary forms. This suggests that renal denervation may be a way to therapeutically reduce salt-preference in high-risk patients.