Analysis of nitric oxide metabolism as a placental or maternal factor underlying the etiology of pre-eclampsia

Gynecol Obstet Invest. 2009;68(4):239-47. doi: 10.1159/000238381. Epub 2009 Sep 17.

Abstract

Background: Defective nitric oxide (NO)-mediated vasodilation is widely regarded as an underlying cause of hypertension in pre-eclampsia, although there are also arguments against this hypothesis.

Methods: We examined both the mRNA levels and the presence of a Glu298Asp substitution in the NO synthase (NOS) gene, as well as the NO metabolite concentration, in placentas and maternal sera from women with pre-eclampsia and in normotensive pregnant controls (25-40 vs. 24-41 weeks of gestation).

Results: Pre-eclamptic and control placentas did not show any significant differences in their NO metabolite levels or their NOS expression levels as measured by quantitative RT-PCR. In addition, we did not find any association between pre-eclampsia and the occurrence of the Glu298Asp amino acid substitution in the NOS gene. In contrast, high maternal circulating NO metabolites were evident in severe pre-eclampsia (p < 0.0001). Although a positive correlation between circulating NO metabolites and blood pressure was not observed, uterine artery resistance measured by ultrasound was found to positively correlate with the maternal NO levels.

Conclusions: Our current data suggest that an altered placental NOS pathway is unlikely to be the primary cause of pre-eclampsia and that the activation of this pathway is possibly in response to maternal symptoms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aspartic Acid / genetics
  • Case-Control Studies
  • Cyclic GMP / blood
  • Female
  • Gestational Age
  • Glutamic Acid / genetics
  • Humans
  • Nitrates / blood
  • Nitric Oxide / blood
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase Type III / genetics
  • Placenta / chemistry*
  • Placenta / enzymology
  • Polymorphism, Single Nucleotide
  • Pre-Eclampsia / enzymology
  • Pre-Eclampsia / etiology*
  • Pregnancy
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Nitrates
  • RNA, Messenger
  • Aspartic Acid
  • Nitric Oxide
  • Glutamic Acid
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • Cyclic GMP