Zhang Wen-Hao, Zhang Xin-Hua
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan City 430071, Hubei Province, P.R. China.
Asian J Androl. 2016 Sep-Oct;18(5):723-31. doi: 10.4103/1008-682X.167721.
Phosphodiesterase isoenzymes 5 inhibitors (PDE5-Is) are the first-line therapy for erectile dysfunction (ED). The constant discoveries of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) cell-signaling pathway for smooth muscle (SM) control in other urogenital tracts (UGTs) make PDE5-Is promising pharmacologic agents against other benign urological diseases. This article reviews the literature and contains some previously unpublished data about characterizations and activities of PDE5 and its inhibitors in treating urological disorders. Scientific discoveries have improved our understanding of cell-signaling pathway in NO/cGMP-mediated SM relaxation in UGTs. Moreover, the clinical applications of PDE5-Is have been widely recognized. On-demand PDE5-Is are efficacious for most cases of ED, while daily-dosing and combination with testosterone are recommended for refractory cases. Soluble guanylate cyclase (sGC) stimulators also have promising role in the management of severe ED conditions. PDE5-Is are also the first rehabilitation strategy for postoperation or postradiotherapy ED for prostate cancer patients. PDE5-Is, especially combined with α-adrenoceptor antagonists, are very effective for benign prostatic hyperplasia (BPH) except on maximum urinary flow rate (Q max ) with tadalafil recently proved for BPH with/without ED. Furthermore, PDE5-Is are currently under various phases of clinical or preclinical researches with promising potential for other urinary and genital illnesses, such as priapism, premature ejaculation, urinary tract calculi, overactive bladder, Peyronie's disease, and female sexual dysfunction. Inhibition of PDE5 is expected to be an effective strategy in treating benign urological diseases. However, further clinical studies and basic researches investigating mechanisms of PDE5-Is in disorders of UGTs are required.
磷酸二酯酶5型同工酶抑制剂（PDE5-Is）是勃起功能障碍（ED）的一线治疗药物。一氧化氮（NO）/环磷酸鸟苷（cGMP）细胞信号通路在其他泌尿生殖道（UGTs）平滑肌（SM）控制方面的不断发现，使PDE5-Is成为治疗其他良性泌尿系统疾病的有前景的药物。本文回顾了相关文献，并包含一些以前未发表的关于PDE5及其抑制剂在治疗泌尿系统疾病方面的特性和活性的数据。科学发现增进了我们对UGTs中NO/cGMP介导的SM舒张细胞信号通路的理解。此外，PDE5-Is的临床应用已得到广泛认可。按需服用PDE5-Is对大多数ED病例有效，而难治性病例建议每日给药并与睾酮联合使用。可溶性鸟苷酸环化酶（sGC）刺激剂在重度ED的治疗中也具有前景。PDE5-Is也是前列腺癌患者术后或放疗后ED的首选康复策略。PDE5-Is，尤其是与α-肾上腺素能受体拮抗剂联合使用时，对良性前列腺增生（BPH）非常有效，但最近证明他达拉非对伴有或不伴有ED的BPH患者的最大尿流率（Q max）无效。此外，PDE5-Is目前正处于针对其他泌尿生殖系统疾病的不同临床或临床前研究阶段，如阴茎异常勃起、早泄、尿路结石、膀胱过度活动症、佩罗尼氏病和女性性功能障碍，具有潜在的应用前景。抑制PDE5有望成为治疗良性泌尿系统疾病的有效策略。然而，还需要进一步的临床研究和基础研究来探究PDE5-Is在UGTs疾病中的作用机制。
