Abstract P169: Renal Denervation Attenuates a Catabolic State in Mice Fed High Salt

Introduction: We recently reported that kidneys accumulate urea as an alternative osmolyte in the renal medulla to concentrate sodium into the urine during high salt intake. This urea-driven water conservation process is coupled with the energy-intensive nature of hepatic urea production, which leads to a catabolic state in mice fed high salt. In this study, we examined the effects of renal denervation on the salt-driven catabolic state since previous studies found that the renal sympathetic nervous system regulates urinary sodium excretion and energy metabolism of some organs such as liver and muscle. Methods: Sham-operated (sham) or renal denervated (RDX) male C57/B6J mice were fed on 0.3% NaCl diet with tap water (NS) or 4% NaCl high salt diet + 0.9% NaCl water to drink (HS) for 4 consecutive weeks (ad libitum), followed by 2 weeks of pair-feeding to match energy intake in all groups. We measured daily food intake and body weight, 24 hours urinary sodium excretion, body sodium content, and activity of liver arginase, a urea producing enzyme. Results: NS + sham and HS + sham mice showed similar body weight gain (NS + sham: +3.6 ± 0.2, HS + sham: +3.4 ± 0.2 g) during ad libitum feeding although HS significantly increased food intake (NS + sham: 3.1 ± 0.04, HS + sham: 3.3 ± 0.04 g/day). After the pair-feeding, HS mice significantly decreased their body weight (NS + sham: +0.9 ± 0.07, HS + sham: -0.6 ± 0.05 g) and increased liver arginase activity (NS + sham: 3792 ± 322, HS + sham: 5412 ± 499 units/L/tissue), confirming the high salt-induced catabolic hepatic urea production. On the other hand, HS did not increase food intake (NS + RDX: 3.2 ± 0.1, HS + RDX: 3.1 ± 0.01 g/day) and liver arginase activity (NS + RDX: 3599 ± 316, HS + RDX: 3363 ± 369 units/L/tissue) in RDX group. In addition, HS + RDX mice did not show pair feeding-induced body weight loss (NS + RDX: +0.6 ± 0.3, HS + RDX: +0.3 ± 0.3 g). HS + RDX mice did not alter 24 hours urinary sodium excretion (HS + sham: 135 ± 6.3, HS + RDX: 142 ± 13 mmol/d/kg) and body sodium content (HS + sham: 0.15 ± 0.003, HS + RDX: 0.15 ± 0.006 mmol/d/kg) compared with HS + sham mice. Conclusion: These findings suggest that renal denervation attenuates the HS-induced body weight loss and catabolic urea production independently of urinary sodium excretion.