Oxygen-related prostaglandin synthesis in ductus arteriosus and other vascular cells.
We compared oxygen-related prostaglandin synthesis in fetal lamb ductus arteriosus (DA) pulmonary artery (PA) and aorta endothelial and smooth muscle cells. We measured basal synthesis of 6-keto-PGF1 alpha and PGE2, the response to calcium ionophore (A23187), a nonspecific stimulus of prostaglandin production, as well as the response to oxygen, a perinatal stimulus, monitoring both the effects of hyperoxia (95% O2) and hypoxia (2% O2). In addition, we established whether differences observed in fetal lamb PA cells related to oxygen tension were also observed in newborn central and microvessel PA cells. Our results indicate that DA endothelial cells increase 6-keto-PGF1 alpha in response to ionophore (p less than 0.05). With hyperoxia, DA endothelial cells increase PGE2 synthesis and DA smooth muscle cells increase 6-keto-PGF1 alpha (p less than 0.05 and 0.02, respectively). Aorta smooth muscle cells increase 6-keto-PGF1 alpha in response to ionophore and hyperoxia (p less than 0.003 and 0.05, respectively). PA endothelial and smooth muscle cells have higher levels of basal prostaglandin synthesis when compared with DA and aorta. In response to ionophore, increased 6-keto-PGF1 alpha is observed in both PA endothelial and smooth muscle cells (p less than 0.02 and 0.0004, respectively), and PGE2 is increased in PA smooth muscle cells (p less than 0.003). Hypoxia, however, decreases PA smooth muscle production of both 6-keto-PGF1 alpha and PGE2 (p less than 0.02 and 0.01, respectively). Similar observations were made in newborn lamb central and microvessel PA cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Rabinovitch
M
M
Division of Cardiology, Hospital for Sick Children, University of Toronto, Ontario, Canada.
Boudreau
N
N
Vella
G
G
Coceani
F
F
Olley
P M
PM
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001011:Aorta / Q000196:embryology / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D004373:Ductus Arteriosus / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010100:Oxygen / Q000008:administration & dosage / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis*; D011651:Pulmonary Artery / Q000196:embryology / Q000378:metabolism; D012756:Sheep
D011453:Prostaglandins; D000001:Calcimycin; D015121:6-Ketoprostaglandin F1 alpha; D015232:Dinoprostone; D010100:Oxygen