The endothelin system is comprised of three active peptides, ET-1, 2, and 3, which are considered to be very powerful vasoconstrictive substances. In humans, endothelins mediate their actions via two specific G-Protein Coupled Receptors, ET_AR and ET_BR. Both ET_AR and ET_BR are present in heart and in human myocardium at similar levels.^1,2

The endothelin receptors differ in their ligand specificity. While ET_AR has varying affinities for the endothelin isoforms (ET-1 >ET-2>ET-3), ET_BR shows no selective affinity.^2,3 Subsequent studies have demonstrated the presence of endothelins in vascular as well as in non-vascular cells and tissues, having multiple biological activities.