Protective effects of Salvia miltiorrhiza on adenine-induced chronic renal failure by regulating the metabolic profiling and modulating the NADPH oxidase/ROS/ERK and TGF-β/Smad signaling pathways.
Compared to SHAM, in CKD aortas EDD and eNOS expression were reduced (<i>p</i> < 0.05) and 3-nitrotyrosine levels were increased, while expression of NADPH oxidase subunits NOX4 and p22<sup>phox</sup> was similar.
Taken together, excessive ROS derived from NADPH oxidase and mitochondria coordinate with RhoA/ROCK activation in a form of positive reciprocal relationship to induce endothelial dysfunction through disturbing endothelium-dependent NO signaling upon IS stimulation in CKD status.
Apoptosis was also increased due to NADPH oxidase gp91 activation and mitochondrial Bax translocation in the proximal end of the jugular vein of CKD rats.
To conclude, the increased activity of NADPH oxidase during CKD is associated with protein modifications which could activate a pathway leading to cardiac remodelling.
Genetic variations in the NADPH/MPO system in chronic kidney disease (CKD) patients might lead to altered activity of these enzymes, and thus to altered risk for oxidative stress (OS) and cardiovascular disease (CVD).