Endothelial nitric oxide synthase deficiency reduces uterine blood flow, spiral artery elongation, and placental oxygenation in pregnant mice

Shathiyah Kulandavelu, Kathie J. Whiteley, Dawei Qu, Junwu Mu, Shannon A. Bainbridge, S. Lee Adamson

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

Preeclampsia is associated with impaired uteroplacental adaptations during pregnancy and abnormalities in the endothelial NO synthase (eNOS)-NO pathway, but whether eNOS deficiency plays a causal role is unknown. Thus, the objective of the current study was to determine the role of eNOS in the mother and/or conceptus in uteroplacental changes during pregnancy using eNOS knockout mice. We quantified uterine artery blood flow using microultrasound, visualized the uteroplacental vasculature using vascular corrosion casts, and used pimonidazole and hypoxia-inducible factor 1a immunohistochemistry as markers of hypoxia in the placentas of eNOS knockout mice versus the background strain, C57Bl/6J (wild type). We found that increases in uteroplacental blood flow, uterine artery diameter, and spiral artery length were reduced, and markers of placental hypoxia in the junctional zone were elevated in late gestation in eNOS knockout mice. Both maternal and conceptus genotypes contributed to changes in uterine artery diameter and flow. Despite placental hypoxia, placental soluble fms-like tyrosine kinase 1 and tumor necrosis factor-α mRNA, and in maternal plasma, soluble fms-like tyrosine kinase 1 were not elevated in eNOS knockout mice. Thus, our results show that both eNOS in the mother and the conceptus contribute to uteroplacental vascular changes and increased uterine arterial blood flow in normal pregnancy.

Original languageEnglish (US)
Pages (from-to)231-238
Number of pages8
JournalHypertension
Volume60
Issue number1
DOIs
StatePublished - Jul 2012
Externally publishedYes

Keywords

  • Blood flow regulation
  • Endothelial NO synthase
  • Hypoxia
  • NO
  • Placenta
  • Preeclampsia/pregnancy

ASJC Scopus subject areas

  • Internal Medicine

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