Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Physiology (Bethesda). 2013 Jul;28(4):262-9. doi: 10.1152/physiol.00001.2013.
Nitric oxide (NO) is the principal mediator of penile erection, and PDE-5 inhibitors are the first-line agents used to treat erectile dysfunction (ED). When NO formation or bioavailability is decreased by oxidative stress and PDE-5 inhibitors are no longer effective, a new class of agents called soluble guanylate cyclase (sGC) stimulators like BAY 41-8543 will induce erection. sGC stimulators bind to the normally reduced, NO-sensitive form of sGC to increase cGMP formation and promote erection. The sGC stimulators produce normal erectile responses when NO formation is inhibited and the nerves innervating the corpora cavernosa are damaged. However, with severe oxidative stress, the heme iron on sGC can be oxidized, rendering the enzyme unresponsive to NO or sGC stimulators. In this pathophysiological situation, another newly developed class of agents called sGC activators can increase the catalytic activity of the oxidized enzyme, increase cGMP formation, and promote erection. The use of newer agents that stimulate or activate sGC to promote erection and treat ED is discussed in this brief review article.
一氧化氮（NO）是阴茎勃起的主要介质，而磷酸二酯酶-5 抑制剂是治疗勃起功能障碍（ED）的一线药物。当氧化应激导致 NO 形成或生物利用度降低，而 PDE-5 抑制剂不再有效时，一种新的药物类别称为可溶性鸟苷酸环化酶（sGC）刺激剂，如 BAY 41-8543，将诱导勃起。sGC 刺激剂与通常处于还原状态、对 NO 敏感的 sGC 结合，增加 cGMP 的形成，促进勃起。当 NO 形成受到抑制且支配海绵体的神经受损时，sGC 刺激剂会产生正常的勃起反应。然而，在严重的氧化应激下，sGC 上的血红素铁可能被氧化，使酶对 NO 或 sGC 刺激剂无反应。在这种病理生理情况下，另一种新开发的药物类别称为 sGC 激活剂，可以增加氧化酶的催化活性，增加 cGMP 的形成，并促进勃起。本文简要综述了使用新型刺激或激活 sGC 的药物来促进勃起和治疗 ED 的情况。
