There are three peptides of endothelial origin, called endothelins (ETs), having different receptors that mediate a potent vasoconstrictor effect and also a mild vasodilation. Their renal effects are characterized by natriuresis in spite of the renal vasoconstriction. This effect, along with the stimulation of ETs by high sodium intake, suggests that ETs may be responsible for maintaining sodium balance when the renin angiotensin system is depressed. ET is activated in deoxycorticosterone acetate (DOCA) salt hypertension models and salt-sensitive hypertension. In humans, the role of ET seems to be similar to that shown in experimental animals; in both, ET participates in the regulation of salt metabolism. Salt-sensitive patients exhibit a blunted renal ET-1 response during sodium load. The role of ETs in humans has been investigated with use of nonspecific ET receptor blockers that inhibit the vasoconstriction and vasodilator components of ET. However, the effects of ET blockade should be investigated with ETA receptor blockers that mediate vasoconstriction alone. Effects of ET blockade should also be evaluated with respect to stimulation of oxidative stress and tissue damage, important mechanisms responsible for tissue fibrosis.