The vascular ET system. Under physiological conditions, majority (80%) of ET-1 produced by endothelial cells is secreted towards the underlying VSMC. The balance of EC ETB and VSMC ETA and ETB receptors in healthy blood vessels is critical for regulation of vascular tone. In diabetes, ET-1 production as well as VSMC ETA and ETB receptors are increased favoring a more contractile and proliferative phenotype leading to complications of diabetes. EC, endothelial cells; NO, nitric oxide, O2●-, superoxide; PGI2, prostacyclin; VSMC, vascular smooth muscle.