Archer Stephen L, Gragasin Ferrante S, Webster Linda, Bochinski Derek, Michelakis Evangelos D
Department of Medicine Cardiology, University of Alberta, Edmonton, Alberta, Canada.
Drugs Aging. 2005;22(10):823-44. doi: 10.2165/00002512-200522100-00003.
The historical basis for understanding erectile function as a neurovascular phenomenon and the advance from fanciful to effective treatment of erectile dysfunction (ED) are reviewed, with emphasis on patients with cardiovascular disease (CVD). ED occurs in 60% of CVD patients by 40 years of age. Male ED and female sexual dysfunction (FSD) diminish quality of life and often warn of occult CVD. ED is often unrecognised but is readily diagnosed during a 5-minute interview using a truncated International Index of Erectile Function questionnaire. Erection of the penis and clitoral engorgement result from local, arousal-induced release of neuronal and endothelial-derived nitric oxide (NO). Arterial vasodilatation and relaxation of cavernosal smooth muscle cells cause arterial blood to flood trabecular spaces, compressing venous drainage, resulting in tumescence. Cyclic guanosine monophosphate (cGMP)-induced activation of protein kinase G mediates the effects of NO by enhancing calcium sequestration and activating large-conductance, calcium-sensitive K+ channels. Future treatment strategies will likely enhance these pathways. Phosphodiesterase-5 inhibitors (sildenafil, tadalafil and vardenafil) increase cGMP levels in erectile tissue. These agents are effective in 80% of CVD patients with ED and can be used safely, even in the presence of stable coronary disease or congestive heart failure, provided nitrates are avoided and patients do not have hypotension, severe aortic stenosis or evocable myocardial ischaemia. Second-line therapies (vacuum constrictor device and transurethral or intracavernosal prostaglandin E1) can also be used in CVD patients. Treatment of FSD and its relationship to CVD are less well established, but similarities to ED exist. ED can be prevented by reduction of CVD risk factors, exercise, weight loss and abstinence from smoking.
本文回顾了将勃起功能理解为神经血管现象的历史基础,以及从幻想式治疗到有效治疗勃起功能障碍(ED)的进展,重点关注心血管疾病(CVD)患者。到40岁时,60%的CVD患者会出现ED。男性ED和女性性功能障碍(FSD)会降低生活质量,并常常警示隐匿性CVD的存在。ED常常未被识别,但使用简化版国际勃起功能指数问卷进行5分钟的问诊就能轻松诊断。阴茎勃起和阴蒂充血是由局部、性唤起诱导的神经元和内皮源性一氧化氮(NO)释放所致。动脉血管舒张和海绵体平滑肌细胞松弛会使动脉血涌入小梁间隙,压迫静脉引流,从而导致肿胀。环磷酸鸟苷(cGMP)诱导的蛋白激酶G激活通过增强钙螯合和激活大电导、钙敏感钾通道来介导NO的作用。未来的治疗策略可能会增强这些途径。磷酸二酯酶-5抑制剂(西地那非、他达拉非和伐地那非)可提高勃起组织中的cGMP水平。这些药物对80%的患有ED的CVD患者有效,并且即使在存在稳定型冠心病或充血性心力衰竭的情况下也可安全使用,前提是避免使用硝酸盐,且患者没有低血压、严重主动脉瓣狭窄或可诱发的心肌缺血。二线治疗(真空收缩装置和经尿道或海绵体内注射前列腺素E1)也可用于CVD患者。FSD的治疗及其与CVD的关系尚未完全明确,但与ED存在相似之处。通过降低CVD危险因素、运动、减肥和戒烟可以预防ED。