Udenafil enhances the recovery of erectile function and ameliorates the pathophysiological consequences of cavernous nerve resection.
BACKGROUND
Radical prostatectomy is the treatment of choice for prostate cancer patients. Despite the introduction of nerve-sparing surgical techniques, its success is not entirely guaranteed and the majority of patients report compromised erectile function following surgical procedures.


OBJECTIVE
This study was performed to investigate the effect of repeated dosing of udenafil, a novel phosphodiesterase type 5 inhibitor, on penile hypoxia and fibrosis induced by bilateral cavernous nerve resection (BCNR) in rats.


METHODS
Thirty male Sprague-Dawley rats (300-320 g) were used in this study. The animals were divided into three groups; group I consisted of sham-operated animals (N = 10), animals in group II underwent BCNR alone (N = 10), and animals in group III were orally treated with 10 mg/kg udenafil b.i.d. for 8 weeks following BCNR (N = 10).


METHODS
The expression of transforming growth factor-beta1, hypoxia-inducible factor-1 alpha, endothelial nitric oxide synthase, neuronal nitric oxide synthase, and endothelin B receptor in penile tissue was examined at gene level. Additionally, erectile function, measured by intracavernous pressure (ICP), and pathological changes in the corpus cavernosum were examined.


RESULTS
While fibrosis, apoptosis, and the expression of TGF-beta1, HIF-1 alpha, and ET(B) were significantly increased, and the expression of eNOS and nNOS were significantly decreased in group II, compared with the sham-operated animals, repeated dosing of udenafil significantly ameliorated these changes. Erectile function was profoundly impaired in animals that underwent BCNR alone, and udenafil treatment significantly attenuated this impairment as measured by ICP.


CONCLUSIONS
These results demonstrate that long-term administration of udenafil ameliorates penile hypoxia and fibrosis induced by cavernous nerve resection. This study also suggests the potential beneficial role of repeated dosing of udenafil in the recovery of erectile function in patients with neuronal erectile dysfunction.
Research Laboratory, Dong-A Pharmaceutical Company, Giheung, Yongin, Gyeonggi 446-905, Korea.
Chan-Ho
CH
Lee
Jee-Hyun
JH
Shin
Gook-Jun
GJ
Ahn
Kyung-Koo
KK
Kang
Byoung-Ok
BO
Ahn
Moohi
M
Yoo
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D005355:Fibrosis; D018783:Impotence, Vasculogenic / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D010410:Penile Erection / Q000187:drug effects*; D011183:Postoperative Complications / Q000188:drug therapy* / Q000209:etiology; D011743:Pyrimidines / Q000627:therapeutic use*; D012313:RNA; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013449:Sulfonamides / Q000627:therapeutic use*; D000096926:Benzenesulfonamides
D011743:Pyrimidines; D012313:RNA; D013449:Sulfonamides; C419664:udenafil; D000096926:Benzenesulfonamides