Angulo J, Cuevas P, Fernández A, Gabancho S, Saenz de Tejada I
Fundación para la Investigación y el Desarrollo en Andrología, Madrid, Spain
Urology. 2001 Mar;57(3):585-9. doi: 10.1016/s0090-4295(00)01032-3.
To analyze the effects of combining an alpha-adrenergic receptor antagonist, phentolamine, with an enhancer of the nitric oxide/cyclic guanosine monophosphate pathway (L-arginine or sildenafil) on neurogenic relaxations of rabbit corpus cavernosum (RCC).
Studies were performed on isolated RCC tissue in organ chambers. Transmural electrical stimulation (TES) was applied at increasing frequencies (0.5 to 6 Hz) on endothelin-contracted RCC strips, and the responses were evaluated.
The activation of alpha(2)-adrenergic receptors with UK 14304 (0.3 microM) significantly inhibited the relaxation induced by TES in RCC strips in which adrenergic neurotransmission was blocked with guanethidine (10 microM). The relaxant responses produced by TES application on RCC strips without guanethidine were not significantly affected by the treatment with L-arginine or sildenafil but were significantly augmented by phentolamine (2.7-fold increase in maximum relaxation). Furthermore, the combinations of phentolamine with L-arginine or sildenafil markedly increased the relaxations evoked by the application of TES in RCC tissue, significantly more than those obtained in the presence of phentolamine alone (4.5 or 4.7-fold increase of maximum relaxation, respectively).
Our results demonstrated a synergistic interaction between the alpha-adrenergic blockade and the potentiation of the nitric oxide/cyclic guanosine monophosphate pathway to increase neurogenic relaxation of trabecular smooth muscle relaxation. This fact suggests that the combination of alpha-adrenergic receptor blockade with L-arginine or sildenafil could represent a therapeutic advantage in the treatment of erectile dysfunction.
分析α-肾上腺素能受体拮抗剂酚妥拉明与一氧化氮/环磷酸鸟苷途径增强剂（L-精氨酸或西地那非）联合应用对兔海绵体神经源性舒张的影响。
在器官浴槽中对分离的兔海绵体组织进行研究。在内皮素预收缩的兔海绵体条带上，以递增频率（0.5至6Hz）施加跨膜电刺激（TES），并评估反应。
用UK 14304（0.3μM）激活α₂-肾上腺素能受体可显著抑制在已用胍乙啶（10μM）阻断肾上腺素能神经传递的兔海绵体条带上由TES诱导的舒张。在未用胍乙啶的兔海绵体条带上，TES诱导的舒张反应不受L-精氨酸或西地那非处理的显著影响，但酚妥拉明可使其显著增强（最大舒张增加2.7倍）。此外，酚妥拉明与L-精氨酸或西地那非联合应用可显著增强兔海绵体组织中TES诱导的舒张，明显超过单独使用酚妥拉明时的效果（最大舒张分别增加4.5倍或4.7倍）。
我们的结果表明，α-肾上腺素能阻断与一氧化氮/环磷酸鸟苷途径增强之间存在协同相互作用，可增强小梁平滑肌的神经源性舒张。这一事实表明，α-肾上腺素能受体阻断与L-精氨酸或西地那非联合应用可能在勃起功能障碍治疗中具有治疗优势。
