Expression of Endothelin-1 and Endothelial Nitric Oxide Synthase in Normal and Preeclamptic Placentae

Khaing, Aung Soe; Swe, Aye Thet; Aung, Lwin Lwin; Thwin, Mya Mya; Sein, Mya Thanda

doi:10.1055/s-0042-1742317

Cited by 2 publications

(1 citation statement)

References 36 publications

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“…Given the interaction between IH and the endothelin system and the circumstantial evidence that the endothelin system is involved in the HDP [23][24][25][26], we hypothesized that increased endothelin-1 and imbalanced ET A R/ET B R signaling serve as key molecular mechanisms underlying IH-induced hypertension during pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Gestational intermittent hypoxia induces endothelial dysfunction and hypertension in pregnant rats: role of endothelin type B receptor

Song,

Yadav,

Dangudubiyyam

et al. 2023

Biology of Reproduction

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Obstructive sleep apnea (OSA) is a recognized risk factor for gestational hypertension, yet the exact mechanism behind this association remains unclear. Here, we tested the hypothesis that intermittent hypoxia (IH), a hallmark of OSA, induces gestational hypertension through perturbed endothelin-1 signaling. Pregnant Sprague–Dawley rats were subjected to normoxia (control), mild IH (mIH, 10.5% O2), or severe IH (sIH, 6.5% O2) from gestational day 10–21. Blood pressure (BP) was monitored. Plasma was collected and mesenteric arteries were isolated for myograph and protein analyses. The mIH and sIH groups demonstrated elevated BP, reduced plasma nitrate/nitrite (NOx), and unchanged endothelin-1 levels compared to the control group. Western blot analysis revealed decreased expression of endothelin type B receptor (ETBR) and phosphorylated endothelial nitric oxide synthase (eNOS), while the levels of endothelin type A receptor (ETAR) and total eNOS remained unchanged following IH exposure. The contractile responses to potassium chloride, phenylephrine, and endothelin-1 were unaffected in endothelium-denuded arteries from mIH and sIH rats. However, mIH and sIH rats exhibited impaired endothelium-dependent vasorelaxation responses to ETBR agonist IRL-1620 and acetylcholine compared to controls. Endothelium denudation abolished IRL-1620-induced vasorelaxation, supporting the involvement of endothelium in ETBR-mediated relaxation. Treatment with IRL-1620 during IH exposure significantly attenuated IH-induced hypertension in pregnant rats. This was associated with elevated circulating NOx levels, enhanced ETBR expression, increased eNOS activation, and improved vasodilation responses. Our data suggested that IH exposure during gestation increases BP in pregnant rats by suppressing ETBR-mediated signaling, providing a molecular mechanism linking IH and gestational hypertension.

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Section: Introductionmentioning

confidence: 99%

Gestational intermittent hypoxia induces endothelial dysfunction and hypertension in pregnant rats: role of endothelin type B receptor

Song,

Yadav,

Dangudubiyyam

et al. 2023

Biology of Reproduction

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Plasma eNOS Concentration in Healthy Pregnancy and in Hypertensive Disorders of Pregnancy: Evidence of Reduced Concentrations in Pre-Eclampsia from Two Independent Studies

Kaihara,

Minami,

Peraçoli

et al. 2023

Diseases

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Hypertensive disorders of pregnancy (HDP), comprising gestational hypertension (GH) and pre-eclampsia (PE), are leading causes of maternal and perinatal morbidity and mortality. Both GH and PE are characterized by new-onset hypertension, but PE additionally includes proteinuria and/or end-organ damage. Impaired nitric oxide (NO) bioavailability may lead to endothelial dysfunction in GH and PE, and the primary source of vascular NO is endothelial NO synthase (eNOS). However, no previous study has investigated plasma eNOS concentrations in patients with GH and PE. In this study, we compared plasma eNOS concentrations in healthy pregnancies and HDP in two independent cohorts. The primary study included 417 subjects, with 43 non-pregnant (NP) and 156 healthy pregnant (HP) women and 122 patients with GH and 96 with PE. The replication study included 85 pregnant women (41 healthy and 44 pre-eclamptic). Plasma concentrations of eNOS were measured using a commercial ELISA kit provided by R&D Systems, and plasma nitrite concentrations were assessed using two ozone-based chemiluminescence assays. Correlations between plasma eNOS concentrations and plasma nitrite concentrations, as well as clinical and biochemical parameters, were evaluated by either Spearman’s or Pearson’s tests. In the primary study, NP women and HDP had significantly lower plasma eNOS concentrations compared to HP; concentrations were even lower in PE compared to GH. Plasma eNOS concentrations were reduced but not significant in early-onset PE, PE with severe features, preterm birth, and intrauterine growth restriction. No correlation was observed between plasma eNOS and nitrite levels. In HDP, there was a significant positive correlation between levels of eNOS and hemoglobin (r = 0.1496, p = 0.0336) as well as newborn weight (r = 0.1487, p = 0.0316). Conversely, a negative correlation between eNOS levels and proteinuria was observed (r = −0.2167, p = 0.0179). The replication study confirmed significantly reduced plasma concentrations of eNOS in PE compared to HP. Our findings provide evidence of reduced plasma eNOS concentrations in HDP; they were particularly lower in PE compared to GH and HP in two independent studies.

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Expression of Endothelin-1 and Endothelial Nitric Oxide Synthase in Normal and Preeclamptic Placentae

Cited by 2 publications

References 36 publications

Gestational intermittent hypoxia induces endothelial dysfunction and hypertension in pregnant rats: role of endothelin type B receptor

Gestational intermittent hypoxia induces endothelial dysfunction and hypertension in pregnant rats: role of endothelin type B receptor

Plasma eNOS Concentration in Healthy Pregnancy and in Hypertensive Disorders of Pregnancy: Evidence of Reduced Concentrations in Pre-Eclampsia from Two Independent Studies

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