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Int. J. Mol. Sci. 2018, 19(6), 1712; https://doi.org/10.3390/ijms19061712

The Impact of the Nitric Oxide (NO)/Soluble Guanylyl Cyclase (sGC) Signaling Cascade on Kidney Health and Disease: A Preclinical Perspective

1
Bayer AG, Cardiovascular Research, Pharma Research Center, 42096 Wuppertal, Germany
2
Division of Nephrology and Clinical Immunology, RWTH Aachen University, 52062 Aachen, Germany
3
Department of Pharmacology, Hannover Medical School, 30625 Hannover, Germany
*
Author to whom correspondence should be addressed.
Received: 15 May 2018 / Revised: 7 June 2018 / Accepted: 8 June 2018 / Published: 9 June 2018
(This article belongs to the Special Issue cGMP-Signalling in Cells: Molecular and Functional Features)
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Abstract

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. View Full-Text
Keywords: nitric oxide; cGMP; chronic kidney disease; soluble guanylyl cyclase; sGC; sGC stimulator; sGC activator nitric oxide; cGMP; chronic kidney disease; soluble guanylyl cyclase; sGC; sGC stimulator; sGC activator
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Krishnan, S.M.; Kraehling, J.R.; Eitner, F.; Bénardeau, A.; Sandner, P. The Impact of the Nitric Oxide (NO)/Soluble Guanylyl Cyclase (sGC) Signaling Cascade on Kidney Health and Disease: A Preclinical Perspective. Int. J. Mol. Sci. 2018, 19, 1712.

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