Influence of Sildenafil on Micturition and Urethral Tone in Ovariectomized and Non‐ovariectomized Mice

Abstract

Nitric oxide synthases (NOSs) and estrogen receptors are expressed in the female urethra. 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). 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. The main outcome measures were micturition behavior, leak point pressure, and histomorphometry. 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. Irrespective of the hormonal status, sildenafil decreased leak point pressure by a nNOS-mediated mechanism.