Topically delivered nitric oxide acts synergistically with an orally administered PDE5 inhibitor in eliciting an erectile response in a rat model of radical prostatectomy.

Patients undergoing radical prostatectomy (RP) have a high incidence of post-operative erectile dysfunction (ED) refractory to treatment by oral phosphodiesterase-type-5-inhibitors (PDE5i). In the present studies, we investigated if a topically applied, nitric oxide microparticle delivery system (NO-MP) might act synergistically with an oral PDE5i (sildenafil) to improve erectile function outcomes in a rat model of RP. Thirty-five Sprague–Dawley rats underwent bilateral transection of the cavernous nerve (CN) for one week. After one-week, animals were orally administered 0, 0.05 or 0.005 mg sildenafil/kg and the erectile response following topical application to the penile shaft of 250mg or 100mg NO-MP, or blank-MP, was monitored over a two-hour timeframe by recording the intracorporal pressure normalized to systemic blood pressure (ICP/BP, N=5 animals/treatment group). Oral treatment with sildenafil by itself resulted in no observable erectile response. However, a combination of orally administered 0.05 sildenafil/kg with topical application of 250mg NO-MP, compared to 250 mg NO-MP by itself, resulted in significantly more spontaneous erections (4.6 compared to 2 erections per hour, t-test; p-value = 0.043), with a significantly faster onset for the first erectile response (11 compared to 22 minutes; t-test, p-value = 0.041). Our results demonstrate a synergistic effect between orally administered PDE5i and topically applied NO-MP in eliciting an erectile response. Furthermore, they suggest a potential novel therapeutic approach to treat men with ED resulting from RP, through combination therapy of a topically applied NO-MP and an orally administered PDE5i.