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. STUDY DESIGN: 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. CONCLUSION: 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.