New conception for the development of hypertension in preeclampsia

Oncotarget. 2016 Nov 29;7(48):78387-78395. doi: 10.18632/oncotarget.13410.

Abstract

Placental vascular dysfunction was suggested to be critical for placental ischemia-initiated hypertension in preeclampsia, although the contributions of endothelium involved are unclear. The present study found, unlike non-placental vessels, acetylcholine showed no vasodilatation effect on placental vessels, indicating that endothelial-derived nitric oxide (NO) was extremely weak in placental vessels. Placental vascular responses to exogenous NO from sodium nitroprusside (SNP) were significantly different from non-placental vessels. These results were further confirmed in sheep, and rat vessels. In preeclamptic placental vessels, acetylcholine also showed no vasodilatation effects, while vascular responses to SNP were suppressed, associated with impaired cGMP/sGC pathway in vascular smooth muscle cells (VSMCs). The current theory on placental ischemia-initiated hypertension in preeclampsia focused on changes in placental vascular functions, including endothelial dysfunction. This study found the placental endothelium contributed very poorly to vasodilatation, and altered vascular functions in preeclampsia mainly occurred in VSMCs instead of endothelial cells. The findings contribute importantly to understanding the special feature of placental vascular functions and its pathophysiological changes in the development of hypertension in preeclampsia.

Keywords: Pathology Section; cGMP/sGC pathway; nitric oxide; placenta; preeclampsia; vascular dysfunction.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Blood Pressure* / drug effects
  • Case-Control Studies
  • Cyclic GMP / metabolism
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology
  • Female
  • Humans
  • In Vitro Techniques
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / physiopathology*
  • Myocytes, Smooth Muscle / metabolism
  • Nitric Oxide / metabolism
  • Placenta / blood supply*
  • Pre-Eclampsia / etiology*
  • Pre-Eclampsia / metabolism
  • Pre-Eclampsia / physiopathology
  • Pregnancy
  • Rats, Sprague-Dawley
  • Sheep, Domestic
  • Soluble Guanylyl Cyclase / metabolism
  • Umbilical Arteries / metabolism
  • Umbilical Arteries / physiopathology
  • Umbilical Veins / metabolism
  • Umbilical Veins / physiopathology
  • Vasodilation* / drug effects
  • Vasodilator Agents / pharmacology

Substances

  • Vasodilator Agents
  • Nitric Oxide
  • Soluble Guanylyl Cyclase
  • Cyclic GMP