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

Authors

  • Xavier Gamé MD,

    Corresponding author
    1. Service d'Urologie, Transplantation Rénale et Andrologie, Centre Hospitalier Universitaire Rangueil, Toulouse, France
    2. Institut National de la Santé et de la Recherche Médicale U858 et Laboratoire de Physiologie, Toulouse, France
    3. Institut Fédératif de Recherche 31, Centre Hospitalier Universitaire Rangueil, Toulouse, France
    Search for more papers by this author
  • Ourdia Bouali MD,

    1. Institut Fédératif de Recherche 31, Centre Hospitalier Universitaire Rangueil, Toulouse, France
    Search for more papers by this author
  • Julien Allard MD,

    1. Institut National de la Santé et de la Recherche Médicale U858 et Laboratoire de Physiologie, Toulouse, France
    Search for more papers by this author
  • Pierre Gourdy MD, PhD,

    1. Institut National de la Santé et de la Recherche Médicale U858 et Laboratoire de Physiologie, Toulouse, France
    Search for more papers by this author
  • Ghislaine Escourrou MD,

    1. Laboratoire D'Anatomie Pathologique, Centre Hospitalier Universitaire Rangueil, Toulouse, France
    Search for more papers by this author
  • Ivan Tack MD, PhD,

    1. Institut National de la Santé et de la Recherche Médicale U858 et Laboratoire de Physiologie, Toulouse, France
    Search for more papers by this author
  • Pascal Rischmann MD,

    1. Service d'Urologie, Transplantation Rénale et Andrologie, Centre Hospitalier Universitaire Rangueil, Toulouse, France
    Search for more papers by this author
  • Jean-François Arnal MD, PhD,

    1. Institut National de la Santé et de la Recherche Médicale U858 et Laboratoire de Physiologie, Toulouse, France
    Search for more papers by this author
  • Bernard Malavaud MD, PhD

    1. Service d'Urologie, Transplantation Rénale et Andrologie, Centre Hospitalier Universitaire Rangueil, Toulouse, France
    Search for more papers by this author

Xavier Gamé, MD, Service d'Urologie, Transplantation Rénale et Andrologie, Centre Hospitalier Universitaire Rangueil, TSA 50032, 31059 Toulouse, France. Tel: +33 561323301; Fax: +33 561323230; E-mail: xaviergame@hotmail.com

ABSTRACT

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. Gamé X, Bouali O, Allard J, Gourdy P, Escourrou G, Tack I, Rischmann P, Arnal J-F, and Malavaud B. Influence of sildenafil on micturition and urethral tone in ovariectomized and non-ovariectomized mice. J Sex Med 2012;9:466–471.

Ancillary