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.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Research Division of Pharmacology, China Pharmaceutical University             College of Life Science and Pharmaceutical Engineering, Nanjing University of Technology, Nanjing, China.
Ming
M
Xu
Yi-Qun
YQ
Tang
De-Zai
DZ
Dai
Yu-Feng
YF
Zheng
Yu-Si
YS
Cheng
Qi
Q
Zhang
Yin
Y
Dai
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000201:enzymology; D005635:Fructosediphosphates / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D051744:Protein Kinase C-epsilon / Q000235:genetics / Q000378:metabolism*; D011687:Purines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation; D014665:Vasodilator Agents / Q000494:pharmacology*
D001786:Blood Glucose; D019332:Endothelin-1; D005635:Fructosediphosphates; D010879:Piperazines; D011687:Purines; D012333:RNA, Messenger; D013450:Sulfones; D014665:Vasodilator Agents; D008315:Malondialdehyde; D000068677:Sildenafil Citrate; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D051744:Protein Kinase C-epsilon; C029063:fructose-1,6-diphosphate