Endothelin receptor antagonists are a class of medications that block the action of endothelin, a potent vasoconstrictor peptide.
Endothelin-1 (ET-1) is a powerful vasoconstrictor that binds to two main receptor types:
ETA receptors – primarily found on vascular smooth muscle cells, causing vasoconstriction and cell proliferation
ETB receptors – found on both endothelial cells promoting vasodilation and smooth muscle cells causing vasoconstriction.
Selective ETA antagonists: Ambrisentan Sitaxentan (withdrawn)
Dual ETA/ETB antagonists: Bosentan Macitentan
Clinical Applications
The primary therapeutic use is in pulmonary arterial hypertension (PAH).
Reduce pulmonary vascular resistance Improve exercise capacity Slow disease progression Improve hemodynamics
Common adverse effects include:
Hepatotoxicity Fluid retention and edema Anemia Teratogenicity Drug interactions
These medications are typically reserved for PAH patients in WHO functional classes II-IV and are often used in combination with other PAH therapies like phosphodiesterase-5 inhibitors or prostacyclin analogs as part of modern combination therapy approaches.