Endothelin antagonism: stepping into the spotlight

Endothelin 1, the most potent endogenous vasoconstrictor, was discovered in 1988,1 followed closely by the identification of its two receptors, endothelin A and endothelin B. Many clinical trials have not shown efficacy of either selective endothelin A or mixed endothelin A and endothelin B antagonists in various cardiovascular diseases2 and the only licensed indications for these agents are pulmonary arterial hypertension and scleroderma digital ulceration, both rare diseases. However, chronic kidney disease might give endothelin antagonists a more common indication.