Effects of selective inhibition of the endothelin A and B receptors on hypoxic pulmonary vasoconstriction in newborn piglets.
The effects on pulmonary artery pressure (PAP) and plasma Endothelin-1 (ET-1) were studied in piglets during severe hypoxemia and reoxygenation for 2 h with selective inhibition of the endothelin receptors. Two groups were subjected to selective ETA (ETA group) or ETB (ETB group) receptor inhibition. During hypoxemia there was an initial increase in PAP to 36.3 and 34.3 mm Hg in the ETA and ETB groups respectively, with a decrease to the end of hypoxemia. During reoxygenation PAP reached a maximum at 5 min with a mean of 29.6 and 38.4 mm Hg in the ETA and ETB groups respectively, and then PAP gradually declined towards baseline. During the 2 h reoxygenation period PAP was higher in the ETB group than in the ETA group (p = 0.02). Plasma ET-1 increased from 1.50 and 1.17 ng/L at baseline to 2.07 and 3.18 ng/L at the end of hypoxemia in the ETA and ETB groups respectively.


CONCLUSIONS
ETB receptor inhibition leads to increased pulmonary vasoconstriction during reoxygenation following hypoxemia compared to ETA receptor inhibition. Not only the ETB receptor, but also the ETA receptor plays a role in maintaining plasma ET-1 levels.
Medbø
S
S
Deptartment of Pediatric Research, Institute for Surgical Research, Department of Gynecology and Obstetrics, National Hospital, Oslo, Norway. sverre.medbo@rh.uio.no
Frøen
J F
JF
Saugstad
O D
OD
D000136:Acid-Base Equilibrium; D000818:Animals; D000831:Animals, Newborn; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood; D006439:Hemodynamics; D000860:Hypoxia / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply*; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011651:Pulmonary Artery / Q000503:physiopathology; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013552:Swine; D014661:Vasoconstriction
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu)