Pathophysiology of hypertension in response to placental ischemia during pregnancy: A central role for endothelin?

Babbette D. LaMarca, Barbara T. Alexander, Jeffery S. Gilbert, Michael J. Ryan, Mona Sedeek, Sydney R. Murphy, Joey P. Granger

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


Background: Preeclampsia is new-onset hypertension with proteinuria during pregnancy. The initiating event in preeclampsia has been postulated to involve reduced placental perfusion, which leads to widespread dysfunction of the maternal vascular endothelium. Objective: The main objective of this brief review was to highlight some of the recent advances in our understanding of the mechanisms whereby the endothelin (ET) system, via ET type A (ETA) receptor activation, modulates blood pressure in preeclamptic women and in animal models of pregnancy-related hypertension. Methods: This review focused on the role of ET and tumor necrosis factor-α (TNF-α) in preeclampsia, with emphasis on the pathophysiology of hypertension in response to placental ischemia in animal models of pregnancy. Relevant published data were identified by searching PubMed and supplemented with contributions from our laboratory. Results: Studies in preeclamptic women indicate that their hypertension is associated with increases in ET synthesis. Recent studies in pregnant rats indicate that the ET system is activated in response to reductions in uterine perfusion pressure and to chronic elevations in serum TNF-α concentrations. In these 2 animal models, the findings also suggest that ET A receptor activation may play a role in mediating hypertension. Conclusions: Although recent studies in animal models implicate an important role for the ET system in preeclampsia, the usefulness of selective ET A receptor antagonists for the treatment of hypertension in women with preeclampsia remains unclear. This important question will not be answered until well-controlled clinical studies using specific ET A receptor antagonists are conducted for women with preeclampsia.

Original languageEnglish (US)
Pages (from-to)S133-S138
JournalGender Medicine
Issue numberSUPPL. 1
StatePublished - 2008
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health (NIH) grants HL38499 and HL51971. NIH National Research Service Awards HL10137-01 and HL78147 supported Dr. Alexander and Dr. LaMarca, respectively.


  • cytokines
  • endothelin
  • hypertension
  • preeclampsia
  • pregnancy


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