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Influence of sildenafil on micturition and urethral tone in ovariectomized and non-ovariectomized mice
Xavier Gamé1, Ourdia Bouali, Julien Allard
1Service d'Urologie, Transplantation Rénale et Andrologie, Centre Hospitalier Universitaire Rangueil, Toulouse, France. xaviergame@hotmail.com
Introduction:
Nitric oxide synthases (NOSs) and estrogen receptors are expressed in the female urethra.
Aim:
We aimed to assess the impact of sildenafil on micturition behavior, urethral tone according to the hormonal status and to determine the implications of the neuronal isoform of NOS (nNOS).
Methods:
Four-week-old C57/BL6 female mice were sham-operated or ovariectomized. Six weeks later, they were injected intraperitoneally by any combination of sildenafil, 7-nitroindazole (7-NI)-a potent selective nNOS inhibitor-or the corresponding vehicles. The mice were then subjected to micturition behavior and leak point pressure studies. Urethral histomorphometry was performed.
Main Outcome Measures:
The main outcome measures were micturition behavior, leak point pressure, and histomorphometry.
Results:
In sham-operated and ovariectomized animals, sildenafil did not impact micturition, although it decreased urethral resistance 10-fold. nNOS inhibition by 7-NI reduced the number of micturitions and increased residual volume and leak point pressure. It abrogated sildenafil-induced drop in urethral resistances. Hormonal status did not influence the structure of the urethral layers.
Conclusions:
Irrespective of the hormonal status, sildenafil decreased leak point pressure by a nNOS-mediated mechanism.
Insights
Sildenafil reduced urethral resistance via a nitric oxide synthase (NOS)-dependent pathway, independent of hormonal status. This mechanism impacts leak point pressure in female mice.
Area of Science:
- Urology
- Pharmacology
- Neuroscience
Background:
- Nitric oxide synthases (NOSs) and estrogen receptors are present in the female urethra.
- Understanding their roles is crucial for female lower urinary tract function.
Purpose of the Study:
- To evaluate sildenafil's effect on micturition and urethral tone.
- To determine the influence of hormonal status on these effects.
- To investigate the role of neuronal NOS (nNOS) in mediating these actions.
Main Methods:
- Female mice (C57/BL6) underwent sham-operation or ovariectomy.
- Mice received sildenafil, a selective nNOS inhibitor (7-nitroindazole/7-NI), or vehicle.
- Micturition behavior, leak point pressure, and urethral histomorphometry were assessed.
Main Results:
- Sildenafil did not alter micturition frequency but significantly reduced urethral resistance.
- nNOS inhibition by 7-NI increased micturition interval and leak point pressure.
- 7-NI abolished the sildenafil-induced decrease in urethral resistance.
- Hormonal status did not affect urethral layer structure.
Conclusions:
- Sildenafil decreases leak point pressure through a mechanism involving nNOS.
- This effect is independent of the animals' hormonal status.
- Findings highlight nNOS as a key mediator in regulating urethral function and sildenafil's action.
