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

Abstract 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...

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Main Authors: Takahiro Imanaka, Kentaro Takezawa, Yuma Kujime, Hiroaki Kitakaze, Go Tsujimura, Sohei Kuribayashi, Yosuke Sekii, Norichika Ueda, Shinichiro Fukuhara, Hiroshi Kiuchi, Hiromitsu Negoro, Norio Nonomura
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Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-86526-6
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author Takahiro Imanaka
Kentaro Takezawa
Yuma Kujime
Hiroaki Kitakaze
Go Tsujimura
Sohei Kuribayashi
Yosuke Sekii
Norichika Ueda
Shinichiro Fukuhara
Hiroshi Kiuchi
Hiromitsu Negoro
Norio Nonomura
author_facet Takahiro Imanaka
Kentaro Takezawa
Yuma Kujime
Hiroaki Kitakaze
Go Tsujimura
Sohei Kuribayashi
Yosuke Sekii
Norichika Ueda
Shinichiro Fukuhara
Hiroshi Kiuchi
Hiromitsu Negoro
Norio Nonomura
author_sort Takahiro Imanaka
collection DOAJ
description Abstract 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 Nω-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.
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spelling doaj-art-973f3e776dcd48bfba741097b9dc92682025-02-02T12:23:21ZengNature PortfolioScientific Reports2045-23222025-01-011511910.1038/s41598-025-86526-6Decreased nitric oxide production is a novel therapeutic target for salt-induced nocturnal polyuria in agingTakahiro Imanaka0Kentaro Takezawa1Yuma Kujime2Hiroaki Kitakaze3Go Tsujimura4Sohei Kuribayashi5Yosuke Sekii6Norichika Ueda7Shinichiro Fukuhara8Hiroshi Kiuchi9Hiromitsu Negoro10Norio Nonomura11Department of Urology, Osaka University Graduate School of MedicineDepartment of Urology, Osaka University Graduate School of MedicineDepartment of Urology, Osaka University Graduate School of MedicineDepartment of Urology, Osaka University Graduate School of MedicineDepartment of Urology, Osaka University Graduate School of MedicineDepartment of Urology, Osaka University Graduate School of MedicineDepartment of Urology, Osaka University Graduate School of MedicineDepartment of Urology, Osaka University Graduate School of MedicineDepartment of Urology, Osaka University Graduate School of MedicineDepartment of Urology, Osaka University Graduate School of MedicineDepartment of Urology, Institute of Medicine, University of TsukubaDepartment of Urology, Osaka University Graduate School of MedicineAbstract 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 Nω-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.https://doi.org/10.1038/s41598-025-86526-6Salt-induced nocturnal polyuriaNitric oxideIntrarenal renin-angiotensin systemAgingModerate-intensity exercise
spellingShingle Takahiro Imanaka
Kentaro Takezawa
Yuma Kujime
Hiroaki Kitakaze
Go Tsujimura
Sohei Kuribayashi
Yosuke Sekii
Norichika Ueda
Shinichiro Fukuhara
Hiroshi Kiuchi
Hiromitsu Negoro
Norio Nonomura
Decreased nitric oxide production is a novel therapeutic target for salt-induced nocturnal polyuria in aging
Scientific Reports
Salt-induced nocturnal polyuria
Nitric oxide
Intrarenal renin-angiotensin system
Aging
Moderate-intensity exercise
title Decreased nitric oxide production is a novel therapeutic target for salt-induced nocturnal polyuria in aging
title_full Decreased nitric oxide production is a novel therapeutic target for salt-induced nocturnal polyuria in aging
title_fullStr Decreased nitric oxide production is a novel therapeutic target for salt-induced nocturnal polyuria in aging
title_full_unstemmed Decreased nitric oxide production is a novel therapeutic target for salt-induced nocturnal polyuria in aging
title_short Decreased nitric oxide production is a novel therapeutic target for salt-induced nocturnal polyuria in aging
title_sort decreased nitric oxide production is a novel therapeutic target for salt induced nocturnal polyuria in aging
topic Salt-induced nocturnal polyuria
Nitric oxide
Intrarenal renin-angiotensin system
Aging
Moderate-intensity exercise
url https://doi.org/10.1038/s41598-025-86526-6
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