Synergy between oral PDE5 inhibitors and topically applied nitric oxide microparticles on the erectile response in a rat model of cavernous nerve injury.

Abstract

This study aimed to evaluate the effectiveness of combining a nitric oxide microparticle delivery system (NO-MP) with various FDA-approved PDE5 inhibitors (PDE5i) for improving erectile responses in a rat model of erectile dysfunction (ED) following cavernous nerve injury, similar to the effects of radical prostatectomy. Male Sprague-Dawley rats, 4-5 months old (weighing ~275 g) underwent bilateral cavernous nerve transection. One week post-surgery animals were administered PDE5i via oral gavage (sildenafil 0.05 mg/kg (N = 9), tadalafil 0.005 mg/kg (N = 8), vardenafil 0.01 mg/kg (N = 7), avanafil 0.1 mg/kg (N = 8) or untreated (N = 5) followed by topical application of 250 mg NO-MP to the penile dermis. Erectile responses were assessed by measuring intracorporeal pressure (ICP) and systemic blood pressure (BP) after the application of NO-MP. Compared to NO-MP alone, combination therapy with a PDE5i significantly (P < 0.05) reduced the time to initial erectile response from 63 ± 21.6 min to 8-23 min (vardenafil: 23 ± 2.3, avanafil: 11 ± 8.1, sildenafil: 19.9 ± 9.8, tadalafil: 18 ± 12.8), and increased the frequency of spontaneous erections from 1 ± 0.71 to 1.7-2.7 per hour (vardenafil: 2.1 ± 0.9, avanafil: 2.7 ± 1.1, sildenafil: 1.7 ± 0.6, tadalafil: 2.5 ± 0.8). No significant changes in maximal ICP/BP, duration of erectile response or baseline ICP/BP were observed. These results suggest that combining NO-MP with PDE5i may provide a promising approach for treating ED after radical prostatectomy.