The endothelin family of peptides are potent vasoconstrictors synthesized by endothelial cells in both constitutive and inducible pathways. The biological actions of endothelins are mediated by two GPCRs, ETA and ETB. Whereas ETA is the predominant receptor on smooth muscle cells and thus is the primary mediator of the vasoconstrictor activity, ETB is found on endothelial cells and mediates vasodilation. In addition, ETB has also been linked to renal failure, congestive heart failure, atherosclerosis, and pulmonary hypertension. A mutation in ETB has been found to cause Hirschsprung disease-2, a degenerative disease of the digestive tract.