Ferrini Monica G, Gonzalez-Cadavid Nestor F, Rajfer Jacob
Department of Health and Life Sciences, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA.
Department of Urology, UCLA School of Medicine, Los Angeles, CA, USA;; Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA.
Transl Androl Urol. 2017 Feb;6(1):20-27. doi: 10.21037/tau.2016.11.18.
Erectile dysfunction (ED) will visit every man at some time in his life. The age at when that knock on the door is heard is totally dependent on one's genetics as well as other extrinsic factors. Unlike guests who come for a visit and then leave, once ED shows up it tends to hang around forever. To add insult to injury, the longer ED hangs around, the worse it will get. It is estimated that by the time a man is in his 40's, he has about a 40% chance of having some form of ED and this prevalence increases about 10% per decade thereafter. This suggests that the aging related process that leads to ED begins early in life. It turns out that the most common cause of ED, regardless of the patient's age, is due to a problem with the vascular system of the penis. However, this specific aging related vascular problem is not caused by arterial disease but due to a dysfunction and/or loss of the corporal smooth muscle cells (SMC), the main constituent of the corporal sinusoids. As one gets older, these SMC continue to degrade and disappear. When approximately 15% of these cells have been impacted, it results in an inability of the corporal tissue to retain and/or prevent the blood from "leaking" out of the corporal sinusoids into the systemic veins. However, the corporal SMC themselves begin to combat this aging process by expressing the inducible nitric oxide synthase (iNOS) enzyme to make nitric oxide (NO) in an attempt to quench the high intracellular oxidative stress responsible for the SMC apoptosis. When this iNOS pathway is then pharmacologically upregulated, reversal of these aging related changes in the corpora with correction of the venous leakage is observed. Since we believe that aging related ED is pathologically the same disorder as essential hypertension, the development of a therapeutic regimen that can halt, delay or possibly reverse the cellular processes that lead to aging related ED should also be applicable to those patients diagnosed with essential hypertension.
勃起功能障碍（ED）在每个男性一生中的某个阶段都会出现。出现这种情况的年龄完全取决于个人的遗传因素以及其他外在因素。与那些来访后就离开的客人不同，一旦ED出现，它往往会一直存在。更糟糕的是，ED持续的时间越长，情况就会越糟。据估计，到男性40多岁时，他患某种形式ED的几率约为40%，此后每十年患病率大约增加10%。这表明导致ED的与衰老相关的过程在生命早期就开始了。事实证明，无论患者年龄如何，ED最常见的原因是阴茎血管系统出现问题。然而，这种与衰老相关的特定血管问题并非由动脉疾病引起，而是由于海绵体窦的主要成分——海绵体平滑肌细胞（SMC）功能障碍和/或缺失。随着年龄的增长，这些SMC持续退化并消失。当大约15%的这些细胞受到影响时，就会导致海绵体组织无法保留和/或阻止血液从海绵体窦“泄漏”到体循环静脉中。然而，海绵体SMC自身开始通过表达诱导型一氧化氮合酶（iNOS）来对抗这种衰老过程，以产生一氧化氮（NO），试图消除导致SMC凋亡的高细胞内氧化应激。当这条iNOS途径通过药理学方法上调时，观察到海绵体中这些与衰老相关的变化得以逆转，静脉漏得到纠正。由于我们认为与衰老相关的ED在病理上与原发性高血压是同一种疾病，那么开发一种能够停止、延缓或可能逆转导致与衰老相关ED的细胞过程的治疗方案，也应该适用于那些被诊断为原发性高血压的患者。
