Increased circulating trimethylamine N-oxide plays a contributory role in the development of endothelial dysfunction and hypertension in the RUPP rat model of preeclampsia

Hypertens Pregnancy. 2019 May;38(2):96-104. doi: 10.1080/10641955.2019.1584630. Epub 2019 Mar 1.

Abstract

We examined whether trimethylamine-N-oxide (TMAO) plays a role in endothelial dysfunction and hypertension in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia (PE). Methods: Normal pregnant rats and RUPP rats were treated without or with 3,3-Dimethyl-1-butanol (DMB, a TMAO inhibitor) from gestational day 14. Results: On day 19 of gestation, RUPP rats had higher plasma TMAO, impaired vasodilation and hypertension, decreased interleukin (IL)-10, increased superoxide production and proinflammatory cytokines in the aorta. All of which were reversed by DMD. Conclusion: Increased circulating TMAO downregulates IL-10 and promotes vascular inflammation and oxidative stress, contributing to endothelial dysfunction and hypertension in PE.

Keywords: Preeclampsia; endothelial dysfunction; hypertension; interleukin-10; trimethylamine N-oxide.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / physiopathology*
  • Female
  • Hexanols
  • Inflammation / blood
  • Interleukin-10 / blood
  • Methylamines / blood*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Pre-Eclampsia / blood*
  • Pre-Eclampsia / enzymology
  • Pre-Eclampsia / physiopathology
  • Pregnancy
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism

Substances

  • Hexanols
  • Methylamines
  • Reactive Oxygen Species
  • Interleukin-10
  • Nitric Oxide
  • 3,3-dimethylbutan-1-ol
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • trimethyloxamine