Reactive oxygen metabolites relax the lamb ductus arteriosus by stimulating prostaglandin production.
To determine whether oxygen metabolites can cause ductus relaxation, we used rings of fetal ductus obtained from 36 near-term lambs and measured the effects of the oxygen metabolites generated by the combination of hypoxanthine and xanthine oxidase. The oxygen metabolites produced by hypoxanthine plus xanthine oxidase caused relaxation of the ductus that was inhibited by catalase (hydrogen peroxide scavenger) but not by superoxide dismutase (superoxide anion scavenger). In addition, hypoxanthine plus xanthine oxidase produced a 14-fold increase in prostaglandin (PG) E2 production with only twofold increase in 6-keto-PGF1 alpha (the stable metabolite of PGI2). PGE2 is the most potent relaxant of the ductus arteriosus. The presence of either catalase or indomethacin blocked both the increase in prostaglandin production and the relaxation. We conclude that reactive oxygen metabolites relax the ductus arteriosus and oppose the normal constriction that occurs after birth. However, the vasoactive effects of reactive oxygen metabolites in the ductus appear to be mediated exclusively through the generation of PGE2.
Clyman
R I
RI
Cardiovascular Research Institute, University of California, San Francisco 94143.
Saugstad
O D
OD
Mauray
F
F
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004373:Ductus Arteriosus / Q000502:physiology*; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009994:Osmolar Concentration; D010100:Oxygen / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D012756:Sheep; D013268:Stimulation, Chemical; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014969:Xanthine Oxidase / Q000494:pharmacology
D007042:Hypoxanthines; D011453:Prostaglandins; D019271:Hypoxanthine; D014969:Xanthine Oxidase; D010100:Oxygen; D007213:Indomethacin