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Attenuated endothelin‐1 mRNA expression with endothelin‐1 receptor blockade during hypoxaemia and reoxygenation in newborn piglets

We investigated the cause of decreased plasma endothelin‐1 (ET‐1) during hypoxaemia and reoxygenation in newborn piglets subjected to simultaneous blocking of the ET‐1 receptors. Changes in plasma ET‐1 and prepro‐ET‐1 mRNA expression in the main pulmonary artery and the left lower lobe in the lung were studied in 1‐2‐d‐old piglets. Ten minutes prior to hypoxaemia, the hypoxaemia group (n = 10) was given saline, two groups (both n = 9) were given 1 and 5 mg/kg i.v. SB 217242 (an ET‐1 receptor antagonist). Two groups served as normoxic controls, with and without SB 217242 5 mg/kg i.v. Hypoxaemia was induced by ventilating with 8% O2 until base excess was 20mmol/l or mean arterial blood pressure was < 20mmHg. Reoxygenation was performed for 2h with room air. During hypoxaemia, plasma ET‐1 decreased in the hypoxaemia group, remained unchanged in the 1‐mg group and increased in the 5‐mg group. At the end of reoxygenation, plasma ET‐1 was above baseline in the 1‐mg and 5‐mg groups. In the pulmonary artery, the hypoxaemia group showed 2‐ to 5‐fold higher prepro‐ET‐1 mRNA expression compared to all the other groups (p < 0.05). There were trends for higher prepro‐ET‐1 mRNA expression in pulmonary tissue in the hypoxaemia group compared to the two receptor‐blocking groups (p < 0.07).