Decreased nitric oxide production is a novel therapeutic target for salt-induced nocturnal polyuria in aging

Nocturnal polyuria is a major cause of nocturia, which affects quality of life. Aging-related decreases in nitric oxide production have been reported to contribute to salt-induced nocturnal polyuria. We posited that enhanced nitric oxide production from exercise could mitigate salt-induced nocturnal polyuria. To validate, we assessed the impact of 4 weeks of moderate-intensity exercise on intrarenal renin-angiotensin system activity and salt-induced polyuria during inactive periods in 80-week-old mice. The moderate-intensity exercise group (Mod-Ex) had increased nitric oxide production and suppressed intrarenal renin-angiotensin system compared to the sedentary group (Sed) (renal angiotensinogen level: Sed vs. Mod-Ex, 1.101 ± 0.077 vs. 0.630 ± 0.048 arbitrary unit, P = 0.002). This exercise also alleviated salt-induced polyuria during inactive periods (diurnal polyuria index: Sed vs. Mod-Ex, 0.292 ± 0.027 vs. 0.193 ± 0.023, P = 0.018). These effects were neutralized by suppression of nitric oxide production by oral administration of N^ω-Nitro-L-arginine methyl ester hydrochloride, an nitric oxide synthesis inhibitor. These findings indicate that exercise-induced improvements in salt-induced polyuria during inactive periods are caused by increases in nitric oxide production. In summary, increasing nitric oxide production may serve as a treatment method for salt-induced nocturnal polyuria in older adults.