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Dual endothelin ET_A and ET_B receptor antagonists are approved therapy for pulmonary artery hypertension (PAH). We hypothesized that ET_B receptor‐mediated clearance of endothelin‐1 at specific vascular sites may compromise this targeted therapy. Concentration‐response curves (CRC) to endothelin‐1 or the ET_B agonist sarafotoxin S6c were constructed, with endothelin receptor antagonists, in various rat and mouse isolated arteries using wire myography or in rat isolated trachea. In rat small mesenteric arteries, bosentan displaced endothelin‐1 CRC competitively indicative of ET_A receptor antagonism. In rat small pulmonary arteries, bosentan 10 μmol L⁻¹ left‐shifted the endothelin‐1 CRC, demonstrating potentiation consistent with antagonism of an ET_B receptor‐mediated endothelin‐1 clearance mechanism. Removal of endothelium or L‐NAME did not alter the EC₅₀ or Emax of endothelin‐1 nor …