Erythropoietin promotes the recovery of erectile function following cavernous nerve injury.
OBJECTIVE
We investigated the effects of recombinant human (rh) erythropoietin (EPO) on erectile function recovery in a rat model of cavernous nerve (CN) injury.


METHODS
Male rats underwent unilateral CN transection and excision of a 5 mm segment of the contralateral CN. One group received rhEPO (5,000 U/kg) subcutaneously daily for 14 days, while another received rhEPO 1 day and 1 hour prior to nerve injury. An additional group of animals was pretreated with 1 dose of darbepoetin (25 microg/kg). At 14 days following CN injury rats underwent erection physiology studies. Axonal regeneration was evaluated by electron microscopy. EPO receptor expression in the penis and major pelvic ganglion was evaluated immunohistochemically and by real-time polymerase chain reaction.


RESULTS
Daily rhEPO effectively recovered erections after CN injury compared with saline treatment. Maximal intracavernous pressure area under the curve normalized to mean arterial pressure was significantly greater in EPO treated vs saline treated animals (p < 0.05). rhEPO and darbepoetin pretreatment was as effective as continuous 14-day therapy. EPO receptor expression was localized to neuronal cell bodies of the major pelvic ganglion, penile nerves and endothelial cells in the penis. Electron microscopy revealed significant improvement in axonal regeneration in rhEPO treated animals 14 days following injury compared to controls.


CONCLUSIONS
EPO receptors are expressed in local neuronal and vascular tissues. Exogenous administration of rhEPO or darbepoetin in the setting of CN injury promotes erectile function recovery. This occurs through axonal regeneration of the injured nerve and possible penile protection.
Allaf
Mohamad E
ME
The James Buchanan Brady Urological Institute, Baltimore, Maryland, USA. mallaf@jhmi.edu
Hoke
Ahmet
A
Burnett
Arthur L
AL
D000704:Analysis of Variance; D000818:Animals; D001483:Base Sequence; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000473:pathology; D004921:Erythropoietin / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D010413:Penis / Q000294:innervation*; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017467:Receptors, Erythropoietin / Q000032:analysis; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin