title: Influence of sildenafil on micturition and urethral tone in ovariectomized and non-ovariectomized mice.
abstract: BACKGROUND
  Nitric oxide synthases (NOSs) and estrogen receptors are expressed in the female urethra.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Service d'Urologie, Transplantation Rénale et Andrologie, Centre Hospitalier Universitaire Rangueil, Toulouse, France. xaviergame@hotmail.com
authors.forename: Xavier
authors.initials: X
authors.lastname: Gamé
authors.forename: Ourdia
authors.initials: O
authors.lastname: Bouali
authors.forename: Julien
authors.initials: J
authors.lastname: Allard
authors.forename: Pierre
authors.initials: P
authors.lastname: Gourdy
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Escourrou
authors.forename: Ivan
authors.initials: I
authors.lastname: Tack
authors.forename: Pascal
authors.initials: P
authors.lastname: Rischmann
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Arnal
authors.forename: Bernard
authors.initials: B
authors.lastname: Malavaud
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007191:Indazoles / Q000494:pharmacology*; D051379:Mice; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010052:Ovariectomy; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D014521:Urethra / Q000187:drug effects* / Q000502:physiology; D014554:Urination / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D007191:Indazoles; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole