Pathophysiology of hypertension in response to placental ischemia during pregnancy: a central role for endothelin?
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-alpha (TNF-alpha) 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-alpha 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.
LaMarca
Babbette D
BD
Department of Physiology, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Alexander
Barbara T
BT
Gilbert
Jeffery S
JS
Ryan
Michael J
MJ
Sedeek
Mona
M
Murphy
Sydney R
SR
Granger
Joey P
JP
D000818:Animals; D004195:Disease Models, Animal; D016232:Endothelins / Q000502:physiology*; D005260:Female; D006801:Humans; D010920:Placenta / Q000098:blood supply; D010927:Placental Insufficiency / Q000503:physiopathology*; D011225:Pre-Eclampsia / Q000503:physiopathology*; D011247:Pregnancy; D044022:Receptor, Endothelin A / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D016232:Endothelins; D044022:Receptor, Endothelin A; D014409:Tumor Necrosis Factor-alpha