Considerable progress has been made during the last two decades in characterizing the pharmacology of the ET-1 signaling pathway with the development of key compounds, such as selective ETA and ETB receptor antagonists (ERAs), dual endothelin receptor/angiotensin receptor antagonists (DARAs), together with selective ETB receptor agonists and radiolabeled analogs to accurately describe the ET system and its role in human and animal models of HTN [13]. This evidence concerns the gene EDN1 and hypertensive disorder.