de Tejada I Sáenz
Fundacion para la Investigacion y el Desarrollo en Andrologia (FI+DA) Madrid, Spain.
Int J Impot Res. 2004 Jun;16 Suppl 1:S40-2. doi: 10.1038/sj.ijir.3901215.
Phosphodiesterase 5 (PDE5) inhibitors prevent the normal hydrolysis of cGMP. As the resulting cGMP accumulation facilitates penile smooth muscle relaxation, PDE5 inhibitors can partially reverse deficiencies in the nitric oxide (NO)/cGMP pathway to treat erectile dysfunction (ED). However, approximately 30-40% of men with ED do not respond to drug therapy. Patients with severe neurologic damage, diabetes mellitus, or severe vascular disease may be resistant to PDE5 inhibitors. Decreased expression or activity of neuronal or endothelial NO synthase (NOS), impaired NO release, or NO destruction will preclude sufficient cGMP formation to permit PDE5 inhibitor efficacy. This article discusses the possible reasons for unresponsiveness and strategies to overcome it. Therapeutic approaches proposed to increase available NO in penile tissue include facilitating NO release by using alpha-2 antagonists, enhancing NO synthesis by providing more substrate for the reaction, and using antioxidants to inhibit NO breakdown by reactive oxygen species.
磷酸二酯酶5（PDE5）抑制剂可阻止环磷酸鸟苷（cGMP）的正常水解。由于由此产生的cGMP积累促进阴茎平滑肌松弛，PDE5抑制剂可部分逆转一氧化氮（NO）/cGMP途径的缺陷，以治疗勃起功能障碍（ED）。然而，约30%-40%的ED男性对药物治疗无反应。患有严重神经损伤、糖尿病或严重血管疾病的患者可能对PDE5抑制剂耐药。神经元或内皮型一氧化氮合酶（NOS）的表达或活性降低、NO释放受损或NO被破坏，将妨碍形成足够的cGMP以实现PDE5抑制剂的疗效。本文讨论了无反应的可能原因及克服方法。提出的增加阴茎组织中可用NO的治疗方法包括使用α-2拮抗剂促进NO释放、通过为反应提供更多底物增强NO合成，以及使用抗氧化剂抑制活性氧对NO的分解。
