Reduction of placental nitric oxide synthase activity in pre-eclampsia

1. The role of the potent vasodilator nitric oxide in the pathogenesis of pre-eclampsia is unclear, We have tested the hypothesis that placental activity of the enzyme which synthesizes nitric oxide (nitric oxide synthase) is reduced in pre-eclampsia. 2. Placentae were obtained after vaginal delivery or Caesarean section from women who had been assigned to the following groups according to standard obstetric criteria: term non-pre-eclamptic control, term pre-eclamptic, preterm non-preeclamptic control and preterm pre-eclamptic. Nitric oxide synthase activity of placental tissue homogenates was assessed by measuring conversion of [H-3]IL-arginine into [H-3]L-citrulline in the presence of NADPH, FAD, tetrahydrobiopterin, calmodulin, CaCl2, magnesium acetate and a range of L-arginine concentrations, Michaelis Menton constants (K-m) amd maximum velocities of reaction (V-max) were calculated using Lineweaver-Burk analysis. 3. V-max was significantly reduced in both term and preterm pre-eclamptic placentae compared with placentae from corresponding gestation-matched controls, There were no significant differences in the Km values for nitric oxide synthase between any of the four groups, nor were V-max or K-m values significantly influenced by mode of delivery. 4. These results provide evidence that human placental nitric oxide synthase activity is significantly reduced in pre-eclampsia, Such a reduction was evident at both term and preterm gestations, Reduced placental nitric oxide synthase activity may have an adverse effect on placental haemodynamic function in pre-eclampsia, and could be involved in the pathogenesis of this important and common obstetric complication.