Bayer AG, Cardiovascular Research, Pharma Research Center, 42096 Wuppertal, Germany.
Division of Nephrology and Clinical Immunology, RWTH Aachen University, 52062 Aachen, Germany.
Int J Mol Sci. 2018 Jun 9;19(6):1712. doi: 10.3390/ijms19061712.
Chronic Kidney Disease (CKD) is a highly prevalent disease with a substantial medical need for new and more efficacious treatments. The Nitric Oxide (NO), soluble guanylyl cyclase (sGC), cyclic guanosine monophosphate (cGMP) signaling cascade regulates various kidney functions. cGMP directly influences renal blood flow, renin secretion, glomerular function, and tubular exchange processes. Downregulation of NO/sGC/cGMP signaling results in severe kidney pathologies such as CKD. Therefore, treatment strategies aiming to maintain or increase cGMP might have beneficial effects for the treatment of progressive kidney diseases. Within this article, we review the NO/sGC/cGMP signaling cascade and its major pharmacological intervention sites. We specifically focus on the currently known effects of cGMP on kidney function parameters. Finally, we summarize the preclinical evidence for kidney protective effects of NO-donors, PDE inhibitors, sGC stimulators, and sGC activators.
慢性肾脏病（CKD）是一种高发疾病，对新的、更有效的治疗方法有巨大的医学需求。一氧化氮（NO）、可溶性鸟苷酸环化酶（sGC）、环鸟苷酸（cGMP）信号级联反应调节着各种肾脏功能。cGMP 直接影响肾血流量、肾素分泌、肾小球功能和管状交换过程。NO/sGC/cGMP 信号转导下调会导致严重的肾脏疾病，如 CKD。因此，旨在维持或增加 cGMP 的治疗策略可能对治疗进行性肾脏疾病具有有益效果。在本文中，我们回顾了 NO/sGC/cGMP 信号级联及其主要的药理学干预部位。我们特别关注 cGMP 对肾功能参数的已知作用。最后，我们总结了 NO 供体、PDE 抑制剂、sGC 激动剂和 sGC 激活剂对肾脏保护作用的临床前证据。
