Endothelin receptor (ETA/ETB, dual)

Class

Dual endothelin receptor antagonist

Endothelin receptors are G protein-coupled receptors, found in two main subtypes—ETA and ETB—that respond to endothelin-1, a peptide produced by the cells lining blood vessels. Endothelin-1 is one of the most potent vasoconstrictors known: when it binds ETA and ETB receptors on vascular smooth muscle, it triggers sustained narrowing of blood vessels and, over time, promotes thickening and proliferation of the vessel wall. This mechanism is central to conditions where blood pressure within a vascular bed becomes pathologically elevated, most notably pulmonary arterial hypertension, where excessive endothelin signaling contributes to remodeling of the lung's small arteries, and in some forms of systemic hypertension that resist standard therapy. Dual endothelin receptor antagonists block both ETA and ETB subtypes on smooth muscle, interrupting this vasoconstrictive and proliferative signal and allowing vessels to relax and remodeling to slow. Because ETB also has counterbalancing roles elsewhere in the vasculature, dual blockade is a deliberate design choice rather than an incidental one, weighed against antagonists that spare ETB. This class of small molecules has become a foundation of therapy for pulmonary vascular disease and is studied in other states of endothelin-driven vascular resistance.