Comparison of sildenafil with strontium fructose diphosphate in improving erectile dysfunction against upregulated cavernosal NADPH oxidase, protein kinase Cε, and endothelin system in diabetic rats.

Phosphodiesterase type 5 inhibitors are potent in relieving erectile dysfunction (ED), however, they are less satisfactory in diabetic patients, probably due to the pro-inflammatory biomarkers caused by diabetes. Therefore, it was interesting to compare the effects of sildenafil with strontium fructose 1,6-diphosphate (FDP-Sr) on cavernosal vascular activity and expressions of pro-inflammatory biomarkers in diabetic rats. Male Sprague-Dawley rats were injected with streptozocin (60 mg/kg, i.p.) to develop diabetes. The animals were diabetic for eight weeks with sildenafil (12 mg/kg per day) or FDP-Sr (200 mg/kg per day) being administered for the last four of those eight weeks. Sildenafil was more effective in relieving reduced vascular dilatation (relevant to ED), but less in attenuating over-expressions of NADPH oxidase p22, p47 and p67 subunits, and ET(A/B) R (endothelin receptor type A and type B) in the diabetic cavernosum. In contrast, FDP-Sr was less effective in improving ED, but more effective in normalizing the abnormal NADPH oxidase and ET(A/B) R. The activated NADPH oxidase and upregulated ET(A) R and ET(B) R due to diabetic lesions played a minor or moderate role in ED. By offering extra ATP, FPD-Sr suppressed these abnormalities, however, sildenafil did not. A combined therapy of sildenafil with FDP-Sr may be more effective in relieving ED in diabetic patients through normalizing pro-inflammatory cytokines and improving the nitric oxide/cGMP pathway in the cavernosum.