The interaction of nitric oxide and superoxide in the human fetal-placental vasculature.
OBJECTIVE
Our purpose was to study the interaction of nitric oxide and superoxide anion on the vasculature of the isolated perfused human placental cotyledon.


METHODS
Isolated placental cotyledons were preconstricted with the thromboxane mimetic U46619, and fetal perfusion pressure was used as an index of response. The interaction of nitric oxide and O2- was studied by three protocols: (1) with endogenous nitric oxide, (2) with addition of exogenous nitric oxide, and (3) with inhibition of nitric oxide synthesis by the nitric oxide synthase inhibitor N-nitro-L-arginine. O2- was generated by infusion of purine-xanthine oxidase. Statistical significance of response to treatment was determined by paired t test.


RESULTS
Infusion of xanthine oxidase with purine in the presence of endogenous nitric oxide resulted in vasodilation (p < 0.05). Vasodilation was more pronounced in the presence of exogenous nitric oxide (p < 0.008). Coinfusion of xanthine oxidase with purine in the presence of N-nitro-L-arginine to inhibit nitric oxide synthesis resulted in vasoconstriction.


CONCLUSIONS
We conclude that, rather than superoxide inactivating nitric oxide, interaction of the two radicals generates in the placental vasculature a vasodilator, which may be peroxynitrite.
Holcberg
G
G
Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, OH 45267-0526, USA.
Kossenjans
W
W
Miodovnik
M
M
Myatt
L
L
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D005333:Fetus / Q000098:blood supply*; D006801:Humans; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D010920:Placenta / Q000098:blood supply*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D013481:Superoxides / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014969:Xanthine Oxidase / Q000494:pharmacology
D011450:Prostaglandin Endoperoxides, Synthetic; D011687:Purines; D014662:Vasoconstrictor Agents; D013481:Superoxides; D019335:Nitroarginine; D009569:Nitric Oxide; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001120:Arginine; D019001:Nitric Oxide Synthase; D014969:Xanthine Oxidase; D000594:Amino Acid Oxidoreductases; C030985:purine