The role of phosphodiesterase type 5 inhibition in the modulation of female
sexual dysfunction was investigated by assessing its effects on in vitro r
elaxation of rabbit clitoris. Stimulation of the nonadrenergic, non-choline
rgic neurons of the clitorus elicited a frequency-dependent relaxation resp
onse. inhibition of NO synthase with L-NAME (100 mu M) or inhibition of sol
uble guanylate cyclase with ODQ (1.0 mu M) almost completely abolished the
electrical field stimulation-induced relaxation of clitorus suggesting that
NO-cGMP pathway mediates the relaxation response to electrical field stimu
lation. Similarly, tetrodotoxin, a neuronal sodium channel blocker abolishe
d the electrical field stimulation-induced clitoral relaxation implying a n
euronal release of NO contributes to the electrical field stimulation elici
ted relaxation. Pretreatment of the clitoral corpus cavernosum strips with
sildenafil (100 nM) enhanced the electrical field stimulation-induced relax
ations both in magnitude and duration. The results suggest that sildenafil
enhances electrical field stimulation elicited clitoral relaxation by a NO-
cGMP dependent pathway. These data also imply that sildenafil may be useful
to treat female sexual dysfunction, (C) 2000 Elsevier Science Inc. All rig
hts reserved.