Influence of sildenafil on micturition and urethral tone in ovariectomized and non-ovariectomized mice.
Résumé
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.