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 hy poxaemia and reoxygenation in newborn piglets subjected to simultaneous blo cking of the ET-1 receptors. Changes in plasma ET-1 and prepro-ET-1 mRNA ex pression in the main pulmonary artery and the left lower lobe in the lung w ere studied in 1-2-d-old piglets. Ten minutes prior to hypoxaemia, the hypo xaemia 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 serv ed as normoxic controls, with and without SE 217242 5 mg/kg i.v. Hypoxaemia was induced by ventilating with 8% O-2 until base excess was <-20 mmol/l o r mean arterial blood pressure was <20 mmHg. Reoxygenation was performed fo r 2 h with room air. During hypoxaemia, plasma ET-1 decreased in the hypoxa emia 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 gr oups (p < 0.05). There were trends for higher prepro-ET-l mRNA expression i n pulmonary tissue in the hypoxaemia group compared to the two receptor-blo cking groups (p < 0.07). Conclusions: We conclude that hypoxaemia and reoxygenation increase prepro- ET-1 mRNA expression in the pulmonary artery in newborn piglets. These obse rvations suggest that the half-life of ET-1 is decreased during hypoxaemia and reoxygenation in newborn piglets.