title: Vaginal lubrication after cervicovaginal stimulation is facilitated by phosphodiesterase type 5 inhibition in ovariectomized mice.
abstract: BACKGROUND
  Nitric oxide synthases (NOSs) and estrogen receptors are expressed in the vagina.
  
  
  OBJECTIVE
  We aimed to assess the impact of sildenafil on vaginal lubrication according to the hormonal status and to determine the role of the neuronal isoform of NOS (nNOS).
  
  
  METHODS
  Four-week-old C57/BL6 female mice were sham operated or ovariectomized. At 10 weeks of age, they were injected intraperitoneally by any combination of sildenafil, 7-nitroindazole (7-NI)--a potent selective nNOS inhibitor--or the corresponding vehicles. Vaginal lubrication was induced in a physiological manner by cervical vaginal probing and quantified depending on the hormonal and pharmacological conditions. The animals were then sacrificed for vaginal histomorphometry.
  
  
  METHODS
  The main outcome measure is the quantification of vaginal transudate after cervicovaginal stimulation and vaginal histomorphometry.
  
  
  RESULTS
  Sildenafil increased cervicovaginal probing-induced vaginal lubrication in ovariectomized and sham-operated animals. Ovariectomized mice exhibited decreased vaginal lubrication as compared with sham-operated mice. When taking into account the presence of severe vaginal atrophy, a threefold increase in transudate per gram of vagina wet weight was revealed in ovariectomized animals. Castration markedly reduced the thickness of the vaginal wall. nNOS inhibition by 7-NI had no impact on vaginal lubrication.
  
  
  CONCLUSIONS
  Irrespective of the hormonal status, sildenafil increased vaginal lubrication. The vaginal effect of sildenafil was independent of the nNOS pathway and more pronounced in ovariectomized animals.
authors.affiliation: Département d'Urologie, Centre Hospitalier Universitaire Rangueil, Toulouse, France. gamexavier@gmail.com
authors.forename: Xavier
authors.initials: X
authors.lastname: Gamé
authors.forename: Mathieu
authors.initials: M
authors.lastname: Roumiguié
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: Catherine
authors.initials: C
authors.lastname: Mazerolles
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; D001284:Atrophy; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005122:Exudates and Transudates / Q000378:metabolism*; D005260:Female; D007191:Indazoles / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D010052:Ovariectomy; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D010812:Physical Stimulation; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D014621:Vagina / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology
chemical_list: D004791:Enzyme Inhibitors; D007191:Indazoles; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; C080122:7-nitroindazole