Martínez-Salamanca Juan I, La Fuente José M, Martínez-Salamanca Eduardo, Fernández Argentina, Pepe-Cardoso Augusto J, Louro Nuno, Carballido Joaquín, Angulo Javier
Servicio de Urología, Hospital Universitario Puerta de Hierro, Madrid, Spain.
Serviço de Urologia, Hospital Santo Antonio, Porto, Portugal.
J Sex Med. 2016 Dec;13(12):1844-1857. doi: 10.1016/j.jsxm.2016.10.005. Epub 2016 Nov 15.
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.
To evaluate the modulation of the α-adrenergic system as a strategy to relieve erectile dysfunction (ED) and functional cavernosal alterations induced by CNI.
A non-selective α-blocker (phentolamine 1 mg/kg daily), a selective α-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.
Erectile responses in vivo in rats and neurogenic contractions and relaxations of rat and human CC.
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.
α-Adrenergic modulation, especially selective α-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.
大鼠海绵体神经损伤（CNI）和男性根治性前列腺切除术（RP）会导致海绵体组织的一氧化氮能功能丧失以及肾上腺素能神经源性收缩增加。
评估α-肾上腺素能系统的调节作用，作为缓解由CNI引起的勃起功能障碍（ED）和海绵体功能改变的一种策略。
双侧挤压性CNI（BCNI）后，口服给予非选择性α受体阻滞剂（酚妥拉明1mg/kg/天）、选择性α受体阻滞剂（西洛多辛[SILOD]0.1mg/kg/天）或赋形剂，持续4周。评估海绵体（CC）的勃起和神经源性反应。还在体内（静脉注射0.03mg/kg）和体外（10nmol/L）评估了SILOD的急性作用。在患有血管性病因ED或RP继发ED的患者的人CC中，测定了SILOD和他达拉非（TAD）对一氧化氮能舒张的影响。
大鼠体内的勃起反应以及大鼠和人CC的神经源性收缩和舒张。
在BCNI大鼠中，长期使用SILOD治疗可显著改善勃起反应，并使急性给予TAD（静脉注射0.3mg/kg）增强勃起反应。SILOD部分恢复了BCNI大鼠CC中的一氧化氮能舒张，并使神经源性收缩恢复正常。长期使用SILOD治疗可部分预防BCNI引起的神经元型一氧化氮合酶表达降低。急性给予SILOD（静脉注射0.03mg/kg）可改善BCNI大鼠体内的勃起反应，并增强体外CC中的一氧化氮能舒张并减少神经源性收缩。在患有血管性病因ED的患者的人CC中，TAD（30nmol/L）、SILOD（10nmol/L）或它们的组合可增加一氧化氮能舒张。RP后ED患者的人CC中TAD的增强作用丧失，但与SILOD联合治疗后恢复。
α-肾上腺素能调节，尤其是选择性α受体阻滞，可改善BCNI后的勃起和海绵体功能。肾上腺素能系统的调节，主要是联合策略，可能在RP后ED的管理中发挥作用。
