Vaginal lubrication after cervicovaginal stimulation is facilitated by phosphodiesterase type 5 inhibition in ovariectomized mice

J Sex Med. 2013 Jun;10(6):1452-60. doi: 10.1111/jsm.12127. Epub 2013 Mar 27.

Abstract

Introduction: Nitric oxide synthases (NOSs) and estrogen receptors are expressed in the vagina.

Aim: 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.

Main outcome measures: 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.

MeSH terms

  • Animals
  • Atrophy
  • Enzyme Inhibitors / pharmacology
  • Exudates and Transudates / metabolism*
  • Female
  • Indazoles / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide Synthase Type I / antagonists & inhibitors
  • Nitric Oxide Synthase Type I / metabolism
  • Ovariectomy*
  • Phosphodiesterase 5 Inhibitors / pharmacology*
  • Physical Stimulation
  • Piperazines / pharmacology*
  • Purines / pharmacology
  • Sildenafil Citrate
  • Sulfones / pharmacology*
  • Vagina / drug effects*
  • Vagina / enzymology
  • Vagina / metabolism
  • Vagina / pathology

Substances

  • Enzyme Inhibitors
  • Indazoles
  • Phosphodiesterase 5 Inhibitors
  • Piperazines
  • Purines
  • Sulfones
  • Sildenafil Citrate
  • Nitric Oxide Synthase Type I
  • Nos1 protein, mouse
  • 7-nitroindazole