INS and endothelial dysfunction: Although the significance of local RAAS may not be fully understood, the increased expression of RAAS components in vascular tissues in animal models of obesity (63, 64), and direct modulation of vascular RAAS in the vasculature in vivo and in vitro by insulin (33, 63), uric acid (65), and estrogens (66), favors the role of vascular RAAS modulating endothelial dysfunction and arterial stiffness.