NOS3 and Hyperglycemia: For instance, hyperglycemia and dyslipidemia can trigger the overexpression of vascular NADPH oxidase for superoxide (O2−) radical generation, leading to the repression of endothelial nitric oxide synthase (eNOS) expression, increased production of a potent vasoconstrictor called endothelin-1 (ET-1), and activation of inflammatory pathways [7,8,9].