Importantly, in preclinical studies of vascular disease, circadian-timed bromocriptine administration to reinstate the natural circadian peak in CNS dopaminergic activity at waking from daily sleep, which is reduced in insulin-resistant states (and causative in its genesis) [1,175], reduced aortic enzymes that potentiate the cellular generation of ROS and endothelial NOS uncoupling, two vascular pathophysiological events induced by a local pro-inflammatory environment and that contribute to endothelial dysfunction and CVD [11]. Here, INS is linked to endothelial dysfunction.