Abstract 12136: Nebivolol Enhances the Efficacy of Type 5 Phosphodiesterase Inhibitors to Relax Human Corpus Cavernosum and Penile Arteries from Diabetic Patients with Erectile Dysfunction
Background: Erectile dysfunction (ED) is highly prevalent among diabetic men. In addition, diabetes is associated with a poorer therapeutic response to conventional therapy for ED, i.e. type 5 phosphodiesterase inhibitors (PDE5-Is), due to impaired NO/cGMP signalling in erectile tissue. Nebivolol is a cardioselective ß1-adrenoceptor antagonist with NO-dependent vasodilatory capacity that has been shown to improve erectile function in diabetic rats with ED. We assessed the hypothesis that nebivolol would enhance relaxant responses and cGMP accumulation induced by PDE5-Is, sildenafil, tadalafil and vardenafil in human corpus cavernosum (HCC) and penile resistance arteries (HPRA) from diabetic ED patients.
Methods: HCC and HPRA were obtained from cavernosal specimens from 15 non-ED,non-diabetic (NEND) organ donors and 17 diabetic patients with ED undergoing penile prosthesis implantation. HCC and HPRA were mounted in organ chambers and wire myographs; respectively, for isometric tension recordings and incubated with nebivolol and/or PDE5-Is. cGMP content in HCC was determined by ELISA.
Results: PDE5-I-induced relaxations (pD2) of HCC and HPRA from diabetic ED patients were reduced vs NEND. Nebivolol (1 µM) potentiated the efficacy of all three PDE5-Is (1 nM - 100 µM) to relax HCC and HPRA in diabetic ED patients (vardenafil did not reach statistical significance). Nebivolol+PDE5-I induced relaxations in diabetic ED patient tissues were equivalent to that observed in PDE5-I treated NEND. Furthermore, nebivolol (1 µM) in combination with PDE5-Is (10 µM) enhanced cGMP accumulation in diabetic HCC; comparable to levels observed in NEND HCC (Table).
Conclusions: Nebivolol improves the efficacy of PDE5-Is to relax HCC and HPRA in diabetic patients with ED likely by enhancing NO/cGMP signalling. Combining PDE5-Is with nebivolol could represent a therapeutic strategy for treating ED in diabetic patients and warrants further clinical investigation.
- © 2011 by American Heart Association, Inc.