Description
A dual ETA/ETB receptor antagonist (IC50s = 0.5 and 391 nM in a radioligand binding assay using recombinant ETA and ETB, respectively); inhibits ET-1-induced intracellular Ca2+ increase in HPASMCs (IC50 = 0.9 nM) and contractions of isolated rat aortic rings (pA2 = 7.6 for ETA) and sarafotoxin S6c-induced contractions of isolated rat tracheal rings (pA2 = 5.9 for ETB); decreases mean arterial blood pressure in DOCA-salt hypertensive rats (ED50 = 1 mg/kg); prevents development of pulmonary hypertension and right ventricle hypertrophy in a rat model of hypertension; decreases the number of vascular and tubule-interstitial lesions and amount of glomerular damage in a rat model of diabetes