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INTRODUCTION AND OBJECTIVES: In addition to a loss of nitrergic function, cavernous nerve injury (CNI) in rats and radical prostatectomy in men result in an enhancement of adrenergic-neurogenic contractions of cavernosal tissue. Our aim was to evaluate the modulation of a-adrenergic system as a strategy to relieve erectile dysfunction (ED) and functional cavernosal alterations induced by CNI in rats. The effects of a-adrenergic blockade on neurogenic relaxation of human corpus cavernosum (HCC) were also evaluated. METHODS: Bilateral crush CNI (BCNI) was induced in anesthetized rats that were randomly selected to receive or not the non-selective a-blocker, phentolamine (1 mg/kg/day; PHENT) or the selective a1A-blocker, silodosine (0.1 mg/kg/day; SILOD) in drinking water for 4 weeks. Erectile responses to cavernosal nerve stimulation and neurogenic responses of corpus cavernosum to electrical field stimulation (EFS) in organ chambers were then evaluated. HCC from ED patients were obtained at the time of penile prosthesis implantation and nitrergic responses to EFS were determined. RESULTS: Chronic treatment with SILOD significantly improved erectile responses, partially recovered nitrergic relaxations and normalized neurogenic contractions (Table). Chronic a-blockade with PHENT or SILOD allowed for a significant potentiation of erectile responses in BCNI rats after acute administration of the PDE5 inhibitor tadalafil (0.3 mg/kg; i.v.). Treatment of HCC with PHENT (1 mM) slightly increased nitrergic relaxations and enhanced the potentiating effects of tadalafil (30 nM) on these responses. CONCLUSIONS: a-adrenergic modulation, especially selective a1A-blockade, improves erectile and cavernosal functions after BCNI. Modulation of adrenergic system, mainly in combination strategies, could have a role in the management of ED after RP.

We investigated the effects of recombinant human (rh) erythropoietin (EPO) on erectile function recovery in a rat model of cavernous nerve (CN) injury.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.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 (p0.05). 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.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.

INTRODUCTION AND OBJECTIVES: RhoA and Rho-kinase (ROCK) are implicated in the inhibition axonal growth/neurite sprouting, and neurodegeneration via regulation of inflammation and apoptosis following peripheral nerve injury. We hypothesize that degeneration of the cavernous nerve (CN) after injury is due to increased RhoA/ROCK signaling in the major pelvic ganglion (MPG) leading to neuronal nitric oxide synthase (nNOS) uncoupling and nerve degeneration. This study aimed to characterize the role of ROCK inhibition in preserving erectile responses, penile contractions, nNOS uncoupling and neurite outgrowth following bilateral cavernous nerve injury (BCNI). METHODS: Male Sprague-Dawleys rats (12 wks) were separated into sham, BCNI and BCNI treated with Y-27632 (ROCK inhibitor, 5 mg/kg twice daily; n1⁄48/group). 14 days after BCNI, groups underwent CN stimulation to determine erectile function. Penes were dissected and contractile responses to phenylephrine (PE) and electrical field stimulation (EFS) were assessed. MPGs were excised and protein (Western blots) and gene expression (q-PCR) of nNOS and growth associated protein 43 (GAP43) were assessed. Additional MPGs (n1⁄43/ group) were cultured in reduced growth factor matrigel for 48h and neurite growth was measured. RESULTS: While erectile function was severely decreased in BCNI rats, daily administration of Y-27632 improved erections 2-fold (p