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-pre-eclamptic control and preterm pre-eclamptic. Nitric oxide synthase activity of placental tissue homogenates was assessed by measuring conversion of [3H]L-arginine into [3H]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 (Vmax) were calculated using Lineweaver-Burk analysis. 3. Vmax 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 K(m) values for nitric oxide synthase between any of the four groups, nor were Vmax 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.
Brennecke
S P
SP
Department of Perinatal Medicine, Royal Women's Hospital, Carlton, Victoria, Australia.
Gude
N M
NM
Di Iulio
J L
JL
King
R G
RG
D001120:Arginine / Q000378:metabolism; D002956:Citrulline / Q000378:metabolism; D046508:Culture Techniques; D005260:Female; D006801:Humans; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D007752:Obstetric Labor, Premature / Q000201:enzymology*; D010920:Placenta / Q000201:enzymology*; D011225:Pre-Eclampsia / Q000201:enzymology*; D011247:Pregnancy
D002956:Citrulline; D001120:Arginine; D019001:Nitric Oxide Synthase