Objectives: Radical prostatectomy is an effective therapy for men with clinically localized prostate cancer. A significant number of men develop erectile dysfunction after radical prostatectomy (PPED) due to intraoperatory cavernous nerve injury causing hypoxia and fibrosis of corpus cavernosus. We established an experimental model of bilateral cavernous neurotomy (BCN) in the rat in order to investigate whether sildenafil treatment in PPED patients could prevent penile tissue damage.
Design and methods: One, 5 and 10 days after neurotomy, animals were treated or not with a single dose of sildenafil (25 mg/kg orally) one hour before sacrifice. To analyze penile oxygenation, rats of each experimental group received (one hour before sacrifice) an intraperitoneal injection of the bio-reductive drug pimonidazole hydrochloride (hypoxyprobeTM-1, 60 mg/Kg), which has been recognized as a standard marker for in vivo imaging and quantification of hypoxia.
Results: With immunohistochemistry for hypoxiprobeTM, we found that BCN induced massive hypoxia at all times investigated in corpora cavernosa sections from the experimental rats, as revealed by computer-assisted quantitative image analysis. This tissue hypo-oxygenation was significantly reduced in sections from sildenafil treated rats at 1 and 5 days after neurotomy, while at 10 days this reduction was less evident and not significant. In addition, functional studies indicated that hypoxic corpora cavernosa tissues were hypersensitive to the relaxant effect of the endothelin receptor type B (ETB) agonist IRL-1620, due to the previously described hypoxia-induced overexpression of ETB receptors. Accordingly, ETB mRNA expression (real time RT-PCR) was significantly increased in corpora cavernosa from BCN rats, and was restored to control levels by sildenafil administration at all times investigated.
Conclusions: Our results indicate that sildenafil treatment can positively influence penile tissue oxygenation after cavernous nerve injury, with its effect being more evident the earlier it is administered.