INS and hypertensive disorder: In humans, (a) insulin stimulates ET-1 production during an euglycemic hyperinsulinemic clamp, (b) insulin resistant patients have elevated plasma ET-1 concentrations (Wolpert et al., 1993), (c) plasma insulin and ET-1 levels correlate in essential hypertensive patients (Zaporowska-Stachowiak et al., 1997), and (d) a mixed ET-1 type A (ETA) and type B (ETB) receptor antagonist produces vasodilation in insulin resistant but not insulin sensitive humans (Shemyakin et al., 2006).