The Endothelin System: A Critical Player in the Pathophysiology of Preeclampsia

  • Joey P. Granger
  • Frank T. Spradley
  • Bhavisha A. Bakrania
Preeclampsia (VD Garovic, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Preeclampsia


Purpose of Review

Preeclampsia (PE) is a disorder of pregnancy typically characterized by new-onset hypertension and proteinuria after gestational week 20. Although preeclampsia is one of the leading causes of maternal and perinatal morbidity and death worldwide, the mechanisms of the pathogenesis of the disorder remain unclear and treatment options are limited. Placental ischemic events and the release of placental factors appear to play a critical role in the pathophysiology. These factors contribute to a generalized systemic vascular endothelial dysfunction and result in increased systemic vascular resistance and hypertension.

Recent Findings

There is increasing evidence to suggest that endothelin-1 (ET-1) in the maternal vascular endothelium is a critical final common pathway, whereby placental ischemic factors cause cardiovascular and renal dysfunction in the mother. Multiple studies report increased levels of ET-1 in PE. A number of experimental models of PE are also associated with elevated tissue levels of prepro-ET-1 mRNA. Moreover, experimental models of PE (placental ischemia, sFlt-1 excess, TNF-α excess, and AT1-AA infusion) have proven to be responsive to ET type A receptor antagonism. Recent studies also suggest that abnormalities in ET type B receptor signaling may also play a role in PE.


Although numerous studies highlight the importance of the ET system in the pathogenesis of PE, further work is needed to determine whether ET receptor antagonists could provide an effective therapy for the management of this disease.


Preeclampsia Pregnancy Hypertension Endothelin Endothelium Placenta Cardiovascular Blood pressure Vascular smooth muscle 



This work was supported by funds in a grant awarded to JPG from the NHLBI (5P01HL051971, 5R01HL108618, 5T32HL105324) and to FTS from NHLBI (4R00HL130577-02).

Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Joey P. Granger
    • 1
    • 2
  • Frank T. Spradley
    • 1
    • 2
    • 3
  • Bhavisha A. Bakrania
    • 1
    • 2
  1. 1.Cardiovascular-Renal Research CenterUniversity of Mississippi Medical CenterJacksonUSA
  2. 2.Department of Physiology & BiophysicsUniversity of Mississippi Medical CenterJacksonUSA
  3. 3.Department of SurgeryUniversity of Mississippi Medical CenterJacksonUSA

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