Thus, endothelial dysfunction with the impairment of NO-dependent vasodilatation can be induced by hyperinsulinemia, excessive ROS and RNS (reactive nitrogen species) production, and it could be amplified by hyperuricemia, inflammation, or activation of the renin–angiotensin system ‘RAS’ [37,38,39,40]. This evidence concerns the gene REN and endothelial dysfunction.