Endothelin binds to two types of receptors found on the blood vessel walls and in tissues: ETA receptors, which are found predominantly in smooth muscle cells in the blood vessels, and ETB receptors, which are also found in fibroblasts, neuronal cells, endothelial cells, and hormone-producing cells.

The activation of the endothelin system plays a critical role in chronic cardiovascular diseases, such as pulmonary hypertension, and in acute cardiovascular conditions, such as right heart failure and cerebral vasospasm, a constriction of blood vessels in the brain following subarachnoid hemorrhage. It is also implicated in connective tissue diseases such as scleroderma and pulmonary fibrosis. Endothelin levels have been shown to correlate with disease severity. Among Actelion's endothelin receptor antagonists are oral, dual ETA-ETB antagonists, and an intravenous selective ETA antagonist for cerebral vasospasm, which block the consequences of excessive endothelin.