Nitric oxide synthase activity in placentae from women with pre-eclampsia

The syncytiotrophoblast (ST) cell layer of the human villous placenta expresses nitric oxide (NO) synthase. Because NO is a potent relaxant of vascular smooth muscle and inhibitor of platelet activity, we postulated that exaggerated intervillous aggregation of platelets and reduced fetoplacental blood flow in pre-eclampsia result from reduced expression of NO synthase (and production of NO) by the ST. Conversion of [H-3]arginine to [H-3]citrulline and Lineweaver-Burk transformation were used to derive the V-max and K-M of NO synthase, Contrary to our expectations, the V,, was not significantly different between villous placenta obtained from nulliparous normal and pre-eclamptic women (n = 11 each). The V-max and K-M were 22.3 +/- 2.3 pmol/mg pet min and 1.3 +/- 0.1 mu m, and 22.0 +/- 2.7 pmol/mg per min and 1.4 +/- 0.1 mu M, for villous placenta from the nulliparous normal and pre-eclamptic women, respectively. The V-max and K-M of placental NO synthase were also comparable among multiparous normal and pre-eclamptic women, as well as women with gestational hypertension. When compared with the enzyme activity of the villous, that of the basal plate was reduced by approximately one-half in all placentae. The calcium-independent activity was consistently 40-fold less than the calcium-dependent activity, and it was similar between villous and basal plate, and between placentae from normal and hypertensive women. We suggest that expression of NO synthase is nob different in placentae obtained from normal and pre-eclamptic women.