Attenuated endothelin- mRNA expression with endothelin- 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 <-20 mmol/l or mean arterial blood pressure was <20 mmHg. Reoxygenation was performed for 2 h 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).


CONCLUSIONS
We conclude that hypoxaemia and reoxygenation increase prepro-ET-1 mRNA expression in the pulmonary artery in newborn piglets. These observations suggest that the half-life of ET-1 is decreased during hypoxaemia and reoxygenation in newborn piglets.
Department of Paediatric Research, Institute for Surgical Research, The National Hospital, Rikshospitalet, Oslo, Norway. sverre.medbo@rh.uio.no
S
S
Medbø
V
V
Beisvag
P A
PA
Tølløfsrud
O
O
Ellingsen
M S
MS
Wright
D000367:Age Factors; D000818:Animals; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood* / Q000235:genetics; D000860:Hypoxia / Q000097:blood*; D008168:Lung / Q000502:physiology; D008969:Molecular Sequence Data; D011651:Pulmonary Artery; D012333:RNA, Messenger / Q000097:blood*; D013552:Swine
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D012333:RNA, Messenger