Cerebral Sympathetic Nervous System Activation Promotes Intrarenal Renin-Angiotensin System Activity and Salt-Induced Nocturnal Polyuria

Purpose This study was aimed at assessing the effects of cerebral sympathetic nervous system activity and renal denervation (RD) on the intrarenal renin-angiotensin system (RAS) and salt-induced nocturnal polyuria (NP). Methods To establish a mouse model, NP was induced by Nω-nitro-L-arginine methyl ester and a high-salt diet. Mice were subjected to dietary, pharmacological, and RD interventions, with blood pressure, urine output, renal norepinephrine, kidney protein expression, and c-Fos positive cells in the hypothalamic paraventricular nucleus (PVN) assessed using standardized physiological, biochemical, and histological methods. Results Renal angiotensinogen (AGT) and PVN c-Fos were significantly increased in NP model mice, indicating sympathetic activation. RD lowered renal AGT and the diurnal polyuria index versus sham (1.070±0.091 vs. 1.595±0.136 arbitrary units, P<0.01; 0.182±0.018 vs. 0.338±0.021, P<0.01). Conclusions Cerebral sympathetic activation may promote intrarenal RAS activity and salt-induced NP; therefore, RD may be a potential therapeutic strategy to improve NP.