Moreland R B
Neurological and Urological Diseases Research, Abbott Laboratories, Abbott Park, Illinois 60064-6118, USA.
Int J Impot Res. 2000 Oct;12 Suppl 4:S39-46. doi: 10.1038/sj.ijir.3900576.
Erectile dysfunction (ED) is estimated to impact more than 150 million men this year worldwide. An understanding of the pathophysiology of ED both furthers the basic scientific knowledge of disease processes and provides a rational design of pharmacotherapy. At present, there are two major views regarding the pathophysiology of ED. In the first hypothesis, the oxygen tension-dependent changes in the penis during erection are proposed to impact corpus cavernosum structure by inducing various cytokines, vasoactive factors and growth factors at the two different oxygen tensions (flaccidity and erection) which, in turn, alter smooth muscle metabolism and connective tissue synthesis. Decreases in the corpus cavernosum smooth muscle/connective tissue ratio have been correlated with an increased likelihood of diffuse venous leak and a failure of the veno-occlusive mechanism in prospective patient studies. Evidence for such a hypothesis incorporates nocturnal penile tumescence and circadian changes in oxygenation as important in maintaining erectile health. The alternate hypothesis proposes that ED is the result of a metabolic imbalance between relaxatory and contractile processes within the trabecular smooth muscle such that contractile processes predominate. Based on this hypothesis, therapy can be accomplished via drugs which shift this balance towards vasodilatation, or by gene therapy approaches to supplement the deficient components favoring smooth muscle relaxation. Both of these hypotheses predict a management strategy for ED that impacts pharmacotherapeutics. In this review of the pathophysiology of ED, each hypothesis will be examined and a synthesis devised incorporating both views. The future of research in this area as well as pharmacotherapy in ED in terms of pathophysiology is discussed including the merits and drawbacks of prophylaxis and prevention of ED. International Journal of Impotence Research (2000) 12, Suppl 4, S39-S46.
据估计，今年全球有超过1.5亿男性受到勃起功能障碍（ED）的影响。了解ED的病理生理学不仅能深化对疾病过程的基础科学认识，还能为药物治疗提供合理的设计思路。目前，关于ED的病理生理学主要有两种观点。在第一种假说中，勃起过程中阴茎内氧张力依赖性变化被认为会通过在两种不同氧张力（疲软和勃起）下诱导各种细胞因子、血管活性因子和生长因子，从而影响海绵体结构，进而改变平滑肌代谢和结缔组织合成。在前瞻性患者研究中，海绵体平滑肌/结缔组织比例的降低与弥漫性静脉漏的可能性增加以及静脉闭塞机制的失效相关。支持这一假说的证据包括夜间阴茎勃起和昼夜氧合变化对维持勃起健康很重要。另一种假说认为，ED是小梁平滑肌舒张和收缩过程之间代谢失衡的结果，导致收缩过程占主导。基于这一假说，可以通过药物使这种平衡向血管舒张方向转变，或者通过基因治疗方法补充有利于平滑肌舒张的缺乏成分来实现治疗。这两种假说都预测了一种影响药物治疗的ED管理策略。在这篇关于ED病理生理学的综述中，将对每种假说进行审视，并设计出一种综合两种观点的方案。还将讨论该领域未来的研究以及ED病理生理学方面的药物治疗，包括ED预防的优缺点。《国际男性性功能障碍研究杂志》（2000年）12卷，增刊4，S39 - S46。
