ZD1611, an Orally Active Endothelin-A Receptor Antagonist, Prevents Chronic Hypoxia-induced Pulmonary Hypertension in the Rat

Endothelin-1 (ET-1) is a potent vasoconstrictor and comitogen implicated in the pathogenesis of pulmonary hypertension (PH). We evaluated the effects of an ETAreceptor-selective antagonist, ZD1611, on hypoxia-induced PH in rats. «Prophylactic» and «therapeutic» paradigms were established in which rats were administered placebo or ZD1611 (1–3 mg/kg, q.i.dpo) concomitant with hypoxic exposure (10% O21 ATM) for 14 days or beginning after 7-day hypoxic exposure for 21 days. Compared with normoxic controls, hypoxic exposure plus placebo increased (P