Women with Preeclampsia have Higher Plasma Endothelin Levels than Women with Normal Pregnancies

Taylor, Robert N.; Varma, Madhu; Teng, Nelson N.H.; Roberts, James M.

doi:10.1210/jcem-71-6-1675

Cited by 324 publications

(96 citation statements)

References 11 publications

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“…Endothelin-1 (ET-1) is a potent vasoconstrictive peptide secreted by endothelial and vascular smooth muscle cells. We 12 and others [13][14][15][16] have shown elevated ET-1 levels in PE. It is possible that endothelial dysfunction induced by the elevated sFLt-1 and sEng levels results in overproduction of ET-1, leading to hypertension and proteinuria.…”

Section: Introductionmentioning

confidence: 59%

The relationship between circulating endothelin-1, soluble fms-like tyrosine kinase-1 and soluble endoglin in preeclampsia

et al. 2011

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Placental overproduction of anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) has a key role in the development of preeclampsia (PE). Circulating endothelin-1 (ET-1) levels are also elevated in PE. In this study, we investigated the correlation between ET-1 and sFlt-1, placental growth factor (PlGF), sEng levels during uncomplicated normotensive pregnancy and PE. A total of 218 pregnant primigravid women were enrolled: 110 with PE and 108 uncomplicated normotensive pregnancies. PE was defined as new onset of elevated blood pressure (BP) 4140/90 mm Hg and X2 þ proteinuria on two occasions after 20 weeks of gestation in previously normotensive pregnant women. Circulating ET-1, sFlt-1, sEng and PlGF levels were estimated using enzyme immunoassays, and correlation between variables was ascertained. Women with PE showed higher levels of sFlt-1 (41.5 ± 15.7 vs 6.15 ± 3.4 ng ml -1 , Po0.001), sEng (84.9 ± 38.8 vs 13.2 ± 6.3 ng ml -1 , Po0.001), ET-1 (1.52 ± 0.55 vs 0.88±0.35 pg ml -1 , Po0.001) and sFlt-1:PlGF ratio (591.1±468.4 vs 18.3±2.1, Po0.001); and lower levels of PlGF (96.3 ± 47.2 vs 497.6 ± 328.2pg ml -1 , Po0.001). BP levels showed an independent relationship with sFlt-1:PlGF ratio in normotensive pregnant women and with sFlt-1:PlGF ratio and ET-1 in PE. sFlt-1 and sFlt-1:PlGF ratio correlated with proteinuria. ET-1 correlated significantly with sFlt-1, sEng and sFlt-1:PlGF ratio in PE. Our results show an association between elevation of sFlt-1 and sEng and ET-1 in the maternal circulation in PE, and strengthen the possibility that ET-1 may be a mediator in genesis of PE syndrome secondary to anti-angiogenic factors released by the placenta.

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Section: Introductionmentioning

confidence: 59%

The relationship between circulating endothelin-1, soluble fms-like tyrosine kinase-1 and soluble endoglin in preeclampsia

et al. 2011

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“…The present results also suggest that the Phe-induced contraction of aortic strips of pregnant rats is enhanced by TNF-␣. On the other hand, preeclampsia is associated with increased plasma levels of endothelin 1 and increased pressor responses to ANG II (40,63). Whether acute treatment with TNF-␣ enhances the vascular contraction to other vasoconstrictors such as endothelin 1 and ANG II and in small resistance vessels with more relevance to preeclampsia is unclear and should represent important areas for future investigation.…”

Section: Discussionmentioning

confidence: 99%

TNF-α enhances contraction and inhibits endothelial NO-cGMP relaxation in systemic vessels of pregnant rats

Giardina

Green

Cockrell

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

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. TNF-␣ enhances contraction and inhibits endothelial NO-cGMP relaxation in systemic vessels of pregnant rats. Am J Physiol Regulatory Integrative Comp Physiol 283: R130-R143, 2002. First published February 28, 2002 10.1152/ajpregu.00704. 2001.-Tumor necrosis factor-␣ (TNF-␣) is elevated in the plasma of preeclamptic women and may have a role in pregnancy-induced hypertension. However, whether the hemodynamic effects of TNF-␣ reflect the direct effects on vascular reactivity is unclear. We tested the hypothesis that TNF-␣ impairs endothelium-dependent relaxation and enhances vascular contraction in systemic vessels of pregnant rats. We measured isometric contraction in aortic strips isolated from virgin and pregnant Sprague-Dawley rats (nontreated vs. treated for 2 h with 10-1,000 pg/ml TNF-␣). In endotheliumintact vascular strips, TNF-␣ caused greater enhancement of phenylephrine (Phe) contraction in pregnant than virgin rats. TNF-␣ caused significant inhibition of ACh-and bradykinin-induced vascular relaxation and nitrite/nitrate production that were more prominent in pregnant than virgin rats. N G -nitro-L-arginine methyl ester [L-NAME, 100 M, an inhibitor of nitric oxide (NO) synthase] or 1H-[1,2,4]oxadiazolo[4,3]-quinoxalin-1-one (ODQ, 1 M, an inhibitor of cGMP production in smooth muscle) inhibited ACh relaxation and enhanced Phe contraction in nontreated but to a lesser extent in TNF-␣-treated vessels, particularly those of pregnant rats. Endothelium removal enhanced Phe contraction in nontreated but not TNF-␣-treated vessels, especially those of pregnant rats. Relaxation of Phe contraction with the NO donor sodium nitroprusside was not different between nontreated and TNF-␣-treated vessels. Thus TNF-␣ enhances vascular contraction and inhibits endothelium-dependent NO-cGMP-mediated vascular relaxation in systemic vessels, particularly those of pregnant rats. The results support a direct role for TNF-␣ as a possible mediator of increased vascular resistance associated with pregnancy-induced hypertension.cytokines; endothelium; nitric oxide; pregnancy; arterial pressure; tumor necrosis factor-␣ NORMAL PREGNANCY IS OFTEN associated with decreased systemic vascular resistance and arterial pressure and reduced vascular reactivity to circulating vasoconstrictors (20,35,46,51). The hemodynamic and vascular changes associated with normal pregnancy have been attributed in part to increased nitric oxide (NO) synthesis by various cells including the vascular endothelial cells (1,18,54,62,69). This is supported by studies showing that the tissue expression and activity of NO synthase (NOS) are enhanced during late gestation (4,13,61,68) and that the metabolic production and plasma level of guanosine 3Ј,5Ј-cyclic monophosphate (cGMP), a second messenger of NO and a cellular mediator of vascular smooth muscle relaxation (30,34), are increased during pregnancy (15).In 5-10% of pregnancies, women develop a condition called preeclampsia, which is characterized by proteinuria, increased intravascular coagulation and sy...

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“…Although some studies have reported no significant changes in circulating levels of ET-1 during moderate forms of preeclampsia, a possible role for ET-1 as a paracrine or autocrine agent in preeclampsia remains worthy of consideration. 11,12,23,46,47 Because ET-1 is released toward the vascular smooth muscle in a paracrine fashion, changes in plasma levels of ET may not reflect its local production. Indeed, this is one of the reasons why it has been difficult to ascertain whether preeclampsia is associated with altered ET production.…”

Section: Endothelinmentioning

confidence: 99%

Recent Progress Toward the Understanding of the Pathophysiology of Hypertension During Preeclampsia

2008

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Women with Preeclampsia have Higher Plasma Endothelin Levels than Women with Normal Pregnancies

Cited by 324 publications

References 11 publications

The relationship between circulating endothelin-1, soluble fms-like tyrosine kinase-1 and soluble endoglin in preeclampsia

The relationship between circulating endothelin-1, soluble fms-like tyrosine kinase-1 and soluble endoglin in preeclampsia

TNF-α enhances contraction and inhibits endothelial NO-cGMP relaxation in systemic vessels of pregnant rats

Recent Progress Toward the Understanding of the Pathophysiology of Hypertension During Preeclampsia

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