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Impaired nitric oxide mechanisms underlying lower urinary tract dysfunction in aging rats
Daisuke Gotoh1,2, Kazumasa Torimoto2, Kenta Onishi2
1Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States.
American Journal of Physiology. Renal Physiology
|September 28, 2023
Summary
Aging rats exhibit lower urinary tract dysfunction due to impaired nitric oxide signaling. This study in aging rat models reveals molecular changes linked to voiding dysfunction, highlighting NO
Area of Science:
- Urology
- Gerontology
- Molecular Biology
Background:
- Aging is associated with lower urinary tract dysfunction (LUTD).
- Nitric oxide (NO) plays a crucial role in regulating bladder and urethral function.
- Understanding age-related molecular changes in LUTD is essential for developing targeted therapies.
Purpose of the Study:
- To investigate bladder and urethral activity in aging rats.
- To examine nitric oxide (NO)-related molecular alterations in aging rats.
- To establish aging rats as a model for age-related LUTD.
Main Methods:
- Comparison of young (12 wk) and aging (15 mo) rats.
- 24-h voiding assays, awake cystometry (CMG), and urethral perfusion pressure (UPP) recordings.
- Assessment of mRNA expression (NO-, ischemia-, inflammation-related markers) and cGMP levels in bladder and urethral tissues.
Main Results:
- Aging rats showed increased non-voiding contractions, post-void residual volume, and decreased voiding efficiency.
- Urethral pressure reduction and high-frequency oscillation (HFO) amplitude were lower in aging rats.
- Aging rats exhibited elevated bladder mRNA levels of Hif-1α, Vegf-a, Tgf-β1, and reduced urethral mRNA levels of Nos1, Prkg1, and cGMP.
Conclusions:
- Aging rats demonstrate significant age-related lower urinary tract dysfunctions.
- Impaired nitric oxide (NO)-mediated transmitter function is a key mechanism in age-related LUTD.
- Aging rats serve as a valuable model for studying the progression of age-related LUTD.
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