NOS3 and obesity due to melanocortin 4 receptor deficiency: Based on accumulating evidence, Davel et al. recently proposed that in normal physiology, the endothelial mineralocorticoid receptor is vasoprotective; however, in the presence of cardiovascular risk factors, such as obesity and diabetes, endothelial mineralocorticoid receptor activation leads to endothelial dysfunction as a result of reduced eNOS activity and NO production, increased oxidative stress via eNOS uncoupling and NOX activation, as well as induced expression of adhesion molecules for inflammatory cells (124).