Extracellular superoxide dismutase localization and activity within the human placenta

Abstract

Maintenance of low vascular tone within the placenta is mediated by nitric oxide (NO). The half-life of NO is very short, as superoxide anion (O 2 tt̄) rapidly inactivates NO to form peroxynitrite. Superoxide dismutases compete with NO for O 2 tt̄. By scavenging O 2 tt̄, superoxide dismutase promotes the vasodilatory action of NO. Extracellular superoxide dismutase (EC-SOD) is present in high concentrations within the extracellular matrix of systemic arteries and has been proposed to mediate vascular smooth muscle tone by increasing NO bioavailability. The localization and activity of EC-SOD within the human placenta has not been determined. Placental EC-SOD may be involved in placental vascular tone, and abnormal activity may lead to pre-eclampsia secondary to increased O 2 −--mediated inactivation of NO. To investigate this possibility, the activity and localization of human placental EC-SOD was determined in normal women, and then compared to pre-eclamptic women. Placental EC-SOD localized within the villous extracellular matrix around arterioles, and there were no differences in distribution between normal and pre-eclamptic women. There were no differences in placental EC-SOD activity between normal and pre-eclamptic subjects in either center (33.7 ± 4.1 versus 33.1 ± 2.5, P=0.6), or peripheral (34.3 ± 5.6 versus 34.0 ± 3.5, P=0.9) samples. EC-SOD localization around villous vessels suggests that EC-SOD serves potentially to protect the fetal vasculature from O 2 −,, in both normal and pre-eclamptic pregnancies. Placental EC-SOD distribution and activity is not different between pre-eclamptic and normal women, suggesting that EC-SOD is not involved in the vascular changes seen in pre-eclampsia.