Novel soluble guanylyl cyclase activators increase glomerular cGMP, induce vasodilation and improve blood flow in the murine kidney.

ABSTRACT:

Background and purpose

Generation of cGMP via NO-sensitive soluble guanylyl cyclase (sGC) has been implicated in the regulation of renal functions. Chronic kidney disease (CKD) is associated with decreased NO bioavailability, increased oxidative stress and oxidation of sGC to its haem-free form, apo-sGC. Apo-sGC cannot be activated by NO, resulting in impaired cGMP signalling that is associated with chronic kidney disease progression. We hypothesised that sGC activators, which activate apo-sGC independently of NO, increase renal cGMP production under conditions of oxidative stress, thereby improving renal blood flow (RBF) and kidney function.

Experimental approach

Two novel sGC activators, runcaciguat and BAY-543, were tested on murine kidney. We measured cGMP levels in real

SUBMITTER: Stehle D 

PROVIDER: S-EPMC9292672 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature