The interaction of nitric oxide and superoxide in the human fetal-placental vasculature.

Abstract

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