Supplements of BH4 or l‐arginine (the substrate of eNOS) favorably manage to couple the eNOS and ameliorate IR‐induced cardiac damage in animals.[51, 52, 53, 54, 55, 56, 57] Increased BH4 levels improve endothelial function in patients with coronary artery disease or hypercholesterolemia.[58, 59, 60] NO shows antioxidative effects within physiological levels.[61, 62] However, the reaction between NO and O2•− may form a detrimental oxidant named peroxynitrite (ONOO−).[63] Administration of NO donors before or during I/R is cardioprotective in in vivo animal models. This evidence concerns the gene NOS3 and Hypercholesterolemia.