Sildenafil augments pelvic nerve-mediated female genital sexual arousal inthe anesthetized rabbit

The NO-cGMP pathway has been implicated in clitoral and vaginal smooth musc le relaxation based on previous immunochemical, biochemical and physiologic studies. There are limited data from in vivo studies demonstrating enhance ment of the genital sexual arousal response by pharmacologic agents influen cing the NO-cGMP pathway, The goal of this study was to investigate if sild enafil, a phosphodiesterase type-5 inhibitor, facilitated female genital se xual arousal in an animal model in response to pelvic nerve stimulation (PN S), Using female New Zealand White rabbits, we measured the following parameter s before, during and after PNS at 4, 16, and 32 Hz: a) hemoglobin concentra tion and oxygen saturation in female genital (vaginal, labial, clitoral) ti ssues by laser oximetry; b) clitoral blood flow by laser Doppler flowmetry; c) vaginal luminal pressure by a balloon catheter pressure transducer; d) vaginal lubrication by tampon, Sildenafil was administered intravenously (0 .21 mu g/kg, 0.42 mu g/kg, 2.1 mu g/kg) to achieve a systemic concentration of 5, 10 and 50 nM, respectively, After 20 minutes, physiologic measuremen ts were repeated. Sildenafil (50 nM) caused a significant increase in genital oxyhemoglobin c oncentration and a significant decrease in genital deoxyhemoglobin concentr ation, Sildenafil also increased the duration of response following PNS, re lative to genital hemoglobin concentration and mean clitoral blood flow, Si ldenafil caused a decrease in vaginal luminal pressure and resulted in an i ncrease in vaginal lubrication. These data indicate that the NO-cGMP pathway is involved in the physiologic mechanism of female genital arousal and that sildenafil facilitates this r esponse in an in vivo animal model.