Search

Introduction: Cavernous nerve injury (CNI) in rats and radical prostatectomy (RP) in men result in loss of nitrergic function and increased adrenergic-neurogenic contractions of cavernosal tissue., Aim: To evaluate the modulation of the α-adrenergic system as a strategy to relieve erectile dysfunction (ED) and functional cavernosal alterations induced by CNI., Methods: A non-selective α-blocker (phentolamine 1 mg/kg daily), a selective α 1A -blocker (silodosin [SILOD] 0.1 mg/kg daily), or vehicle was orally administered for 4 weeks after bilateral crush CNI (BCNI). Erectile and neurogenic responses of the corpus cavernosum (CC) were evaluated. The acute effects of SILOD also were evaluated in vivo (0.03 mg/kg intravenously) and ex vivo (10 nmol/L). The effects of SILOD and tadalafil (TAD) on nitrergic relaxations were determined in human CC from patients with ED with a vascular etiology or ED secondary to RP., Main Outcome Measures: Erectile responses in vivo in rats and neurogenic contractions and relaxations of rat and human CC., Results: Long-term treatment with SILOD significantly improved erectile responses and allowed for the potentiation of erectile responses by acute treatment with TAD (0.3 mg/kg intravenously) in rats with BCNI. SILOD partly recovered nitrergic relaxations and normalized neurogenic contractions in CC from rats with BCNI. Long-term treatment with SILOD partly prevented BCNI-induced decreases in neuronal nitric oxide synthase expression. Acute administration of SILOD (0.03 mg/kg intravenously) improved erectile responses in vivo and potentiated nitrergic relaxation and decreased neurogenic contractions ex vivo in CC from rats with BCNI. In human CC from patients with ED with a vascular etiology, TAD (30 nmol/L), SILOD (10 nmol/L), or their combination increased nitrergic relaxations. Potentiation by TAD was lost in human CC from patients with ED after RP but was recovered after co-treatment with SILOD., Conclusion: α-Adrenergic modulation, especially selective α 1A -blockade, improves erectile and cavernosal functions after BCNI. Modulation of the adrenergic system, mainly in combination strategies, could have a role in the management of ED after RP., (Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Radical prostatectomy (RP) frequently results in erectile dysfunction (ED). It has been hypothesized that alterations of cavernosal tissue subsequent to RP contribute to ED but functional evaluation of the impact of RP on human erectile structures is lacking., Aim: This study aims to evaluate endothelial function of human corpus cavernosum (HCC) and human penile resistance arteries (HPRA) and neurogenic responses of HCC from patients with ED secondary to RP (ED-RP)., Methods: HCC strips and HPRA were obtained from organ donors without history of ED (No-ED) and patients with ED who were segregated depending on ED etiology: ED-RP or vasculogenic (ED-VASC). Functional evaluation of HCC and HPRA was performed in organ chambers and wire myographs, respectively. Histological evaluation of cavernosal tissue consisted of trichrome staining for fibrosis quantification and TUNEL assay for determination of apoptosis., Main Outcome Measures: Endothelium-dependent and endothelium-independent relaxation, electrical field stimulation (EFS)-induced neurogenic contraction and relaxation, and cavernosal fibrosis and apoptosis., Results: Endothelium-dependent relaxations were significantly impaired in HCC and HPRA from ED-VASC patients while these responses in ED-PR patients were not different to No-ED. Similarly, sildenafil-induced relaxations were reduced in HCC and HPRA from ED-VASC but were preserved in ED-RP. Adrenergic contractions induced by EFS in HCC were potentiated in both ED-RP and ED-VASC. EFS-induced nitrergic relaxation was significantly reduced in HCC from ED-VASC but was almost abolished in ED-RP. Fibrous tissue content and cavernosal apoptosis in HCC from ED-RP were not significantly different from No-ED., Conclusions: Endothelial function and cavernosal sensitivity to phosphodiesterase type 5 inhibitors are preserved in erectile tissue from ED-RP while a marked imbalance in neurogenic modulation of cavernosal tone favoring adrenergic contractile responses over nitrergic relaxation is manifested. Fibrotic and apoptotic processes in cavernosal tissue are not specifically associated to ED-RP. These evidences could help to retarget therapeutic strategies in the management of ED after RP., (© 2014 International Society for Sexual Medicine.)