Intracavernosal onabotulinumtoxin a exerts a synergistic pro-erectile effect when combined with sildenafil in spontaneously hypertensive rats

Abstract

<h3>Objectives</h3> Our overall aim was to provide experimental pharmacological evidence for the use of intracavernosal (ic) onabotulinumtoxinA alone or in combination with phosphodiesterase type 5 inhibitors for difficult-to-treat erectile dysfunction. We thus compared the effects of botulinum toxin A alone and botulinum toxin A combined with phosphodiesterase type 5 inhibitor, and a placebo treatment. <h3>Methods</h3> Erectile function was evaluated following cavernous nerve electrical stimulation at different frequencies in 4 groups (n = 8 / group) of anesthetized, spontaneously hypertensive rats. Rats were treated by onabotulinumtoxinA 10U or saline ic 1 week prior to erectile function testing and sildenafil (0.3 mg/kg) or saline iv 4 minutes prior to testing. Frequency-response curves were compared with a two-way ANOVA. <h3>Results</h3> Intracavernosal pressure/mean arterial pressure ratios were significantly increased by sildenafil and onabotulinumtoxinA ic versus the control condition. OnabotulinumtoxinA 10U ic combined with sildenafil significantly potentiated erectile responses. Area under the curve/mean arterial pressure ratio increased by 19% with sildenafil, by 15% with onabotulinumtoxinA ic and by 58% with the combined treatment. <h3>Conclusions</h3> Both onabotulinumtoxinA ic, and sildenafil, significantly improved erectile responses in spontaneously hypertensive rats, however the effect was greatly amplified when the treatments were combined. These results support further studies into the mechanisms behind the pro-erectile effect of BTX-A ic, as well as multicenter randomized control trials to evaluate the safety and efficacy of BTX-A combined with sildenafil for difficult-to-treat ED. <h3>Conflicts of Interest</h3> No conflict of interest