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March 29, 2026International Neurourology Journal0 citationsOpen Access

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

GTGo TsujimuraKTKentaro TakezawaTWTeppei Wakita

Key Result

Renal denervation significantly reduced the diurnal polyuria index (0.182 vs. 0.338) and renal angiotensinogen levels (1.070 vs. 1.595) compared to sham in a mouse model of nocturnal polyuria.

Key Points

  • This study aims to evaluate the impact of cerebral sympathetic nervous system activity on renal function and nocturnal polyuria.
  • Induced nocturnal polyuria in mice using a high-salt diet and specific pharmacological agents.
  • Conducted renal denervation and monitored parameters including blood pressure and urine output.
  • Assessed renal norepinephrine levels and protein expression in kidneys using biochemical and histological analysis.
  • Increased levels of renal angiotensinogen and c-Fos in the hypothalamic paraventricular nucleus were observed in nocturnal polyuria model mice.
  • Renal denervation significantly reduced renal angiotensinogen levels and improved diurnal polyuria index, indicating a therapeutic effect.

Structured PICO

Does renal denervation reduce intrarenal renin-angiotensin system activity and salt-induced nocturnal polyuria in a mouse model?

P
Population
Male C57BL/6J mice with nocturnal polyuria induced by Nω-nitro-L-arginine methyl ester (L-NAME) and a 1% high-salt diet
I
Intervention
Renal denervation (RD)
C
Comparator
Sham procedure
O
Outcome
Intrarenal renin-angiotensin system (RAS) activity (renal angiotensinogen levels) and diurnal polyuria index (DPi)surrogate

In a mouse model, renal denervation suppressed intrarenal renin-angiotensin system activity and improved salt-induced nocturnal polyuria, suggesting a potential therapeutic mechanism targeting sympathetic overactivity.

Main Result

Absolute Event Rate: 0.182% vs 0.338%

p-value: p=<0.01

Limitations

  • Clinical NP arises from complex physiological and behavioral factors, so findings may explain only part of the pathophysiology.
  • Did not include direct assessment of vasopressin levels.
  • Efficacy of RD in NP of other etiologies remains unclear.

Abstract

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.

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Cite This Study

Tsujimura et al. (2026) studied Nocturnal polyuria. Renal denervation vs. Sham surgery was evaluated on Diurnal polyuria index (DPi) (p=<0.01). Renal denervation significantly reduced the diurnal polyuria index (0.182 vs. 0.338) and renal angiotensinogen levels (1.070 vs. 1.595) compared to sham in a mouse model of nocturnal polyuria.

synapsesocial.com/papers/69c8c35cde0f0f753b39e102https://doi.org/10.5213/inj.2550326.163
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