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

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.