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Endothelin receptor antagonists are approved for pulmonary arterial hypertension. Development of selective ET_A-receptor antagonists over mixed or dual receptor antagonists has depended on a range of receptor binding assays, second messenger assays and functional blood vessel assays. This study compared the 3 clinically-approved endothelin receptor antagonists in assays of human isolated pulmonary and radial arteries in vitro.

Human isolated pulmonary (i.d. 5.5 mm) and human radial (i.d. 3.23 mm) artery ring segments were mounted in organ baths for isometric force measurement. Single concentration-contraction curves to endothelin-1 were constructed in the absence or presence of bosentan (1–10 µM), macitentan (0.03–0.3 µM) or ambrisentan (0.1–1 µM).

All 3 endothelin antagonists caused competitive rightward shifts in the endothelin-1 concentration-response curves in …