Endothelin Type A Receptor Blockade Attenuates the Hypertension in Response to Chronic Reductions in Uterine Perfusion Pressure

Alexander, Barbara T.; Rinewalt, Anna N; Cockrell, Kathy; Massey, Matthew B; Bennett, William A.; Granger, Joey P.

doi:10.1161/01.hyp.37.2.485

Cited by 141 publications

(141 citation statements)

References 32 publications

Supporting

Mentioning

133

Contrasting

Order By: Relevance

“…There is also evidence that ET-1, via ET A receptor activation, causes hypertension observed in pregnant rats and pre-eclamptic women with chronically reduced uterine perfusion pressure. 24,25 Pharmacological studies confirm the important role of the ET A receptor in BP regulation. Selective ET A antagonists such as BQ 123, BMS 182874 and FR 139317 block the rise of BP in certain rat models, which shows that hypertension is to some extent dependent on endothelin-related mechanisms.…”

Section: Discussionmentioning

confidence: 84%

Common genetic variation in the type A endothelin-1 receptor is associated with ambulatory blood pressure: a family study

et al. 2008

View full text Add to dashboard Cite

The endothelins are among the most potent vasoconstrictors known. Pharmacological inhibition of endothelin receptors lowers blood pressure (BP). It is unknown whether naturally occurring genetic variation in the endothelin receptors influences BP. We have evaluated the type A endothelin receptor (EDNRA) as a candidate gene for hypertension in a large family study. A total of 1425 members of 248 families selected via a proband with hypertension were studied. Ambulatory BP monitoring was conducted using the A&D TM2421 device. Four haplotype-tagging single nucleotide polymorphisms (SNPs) spanning the EDNRA gene were typed. There was evidence of association between genotype at the rs5335 (C þ 70G) SNP and night systolic blood pressure ( þ 1.24% (s.e. 0.64) per G allele; P ¼ 0.05); night diastolic blood pressure ( þ 1.64% (s.e. 0.71) per G allele; P ¼ 0.021) and night mean BP ( þ 1.51% (s.e. 0.64) per G allele; P ¼ 0.017). Borderline significant trends in the same direction were seen for daytime BPs. Proportions of hypertensives in each of the three genotype groups were C/C 34.7%, C/G 37.9%, G/G 42.4% yielding an odds ratio for hypertension per G allele of 1.19 (95% confidence interval 1.00-1.41; P ¼ 0.05). In conclusion, the rs5335 (C þ 70G) polymorphism of the EDNRA gene has small effects on the risk of hypertension. Natural variation in other genes in the endothelin-signalling pathway should be explored to identify additional influences on BP regulation.

show abstract

Section: Discussionmentioning

confidence: 84%

Common genetic variation in the type A endothelin-1 receptor is associated with ambulatory blood pressure: a family study

et al. 2008

View full text Add to dashboard Cite

show abstract

“…18,19 Pregnant rats developed hypertension and increased circulating ET-1 levels when subjected to chronic reductions in uteroplacental perfusion pressure. 20 This hypertension was abolished by selective blockade of the ET-1 type A receptor. Exposure of human umbilical vein endothelial cell cultures to sera collected from reductions in uteroplacental perfusion pressure was followed by an increase in the ET-1 concentration in the media, whereas no such increase was noted when cells were exposed to sera from normal pregnant rats, suggesting that a substance present in the PE sera induced ET-1 synthesis.…”

Section: Discussionmentioning

confidence: 95%

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

et al. 2011

View full text Add to dashboard Cite

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.

show abstract

“…48 Using an RNase protection assay, they found that renal expression of preproendothelin was significantly elevated in both the medulla and the cortex of pregnant rats with chronic reductions in uterine perfusion pressure (RUPP) compared with control pregnant rats. Moreover, they reported that chronic administration of the selective ET A receptor antagonist, ABT627 markedly attenuated the increase in mean arterial pressure in pregnant rats with RUPP.…”

Section: Endothelinmentioning

confidence: 99%

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

2008

Self Cite

View full text Add to dashboard Cite

Endothelin Type A Receptor Blockade Attenuates the Hypertension in Response to Chronic Reductions in Uterine Perfusion Pressure

Cited by 141 publications

References 32 publications

Common genetic variation in the type A endothelin-1 receptor is associated with ambulatory blood pressure: a family study

Common genetic variation in the type A endothelin-1 receptor is associated with ambulatory blood pressure: a family study

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

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

Contact Info

Product

Resources

About