They were equal in contribution to the paper.
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
Version of Record online: 18 NOV 2011
© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society
Journal of Pharmacy and Pharmacology
Volume 64, Issue 2, pages 244–251, February 2012
How to Cite
Xu, M., Tang, Y.-Q., Dai, D.-Z., Zheng, Y.-F., Cheng, Y.-S., Zhang, Q. and Dai, Y. (2012), 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. Journal of Pharmacy and Pharmacology, 64: 244–251. doi: 10.1111/j.2042-7158.2011.01390.x
- Issue online: 4 JAN 2012
- Version of Record online: 18 NOV 2011
- Received June 20, 2011; Accepted September 22, 2011
- corpus cavernosum;
- erectile dysfunction;
- endothelin-1 (ED-1);
- strontium fructose diphosphate (FDP-Sr);
- NADPH oxidase
Objectives 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.
Methods 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.
Key findings 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 ETA/BR (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 ETA/BR.
Conclusions The activated NADPH oxidase and upregulated ETAR and ETBR 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.