ArticleHypertension (Dallas, Tex. : 1979)2014
Downregulation of microvascular endothelial type B endothelin receptor is a central vascular mechanism in hypertensive pregnancy.
Article in Hypertension (Dallas, Tex. : 1979), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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48 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Reduced uterine perfusion pressure as a model for preeclampsia and fetal growth restriction in murine: a systematic review and meta-analysis.American journal of physiology. Heart and circulatory physiology · 2024Pooled it
- Prenatal aspirin use is associated with preserved vascular endothelial function measured after pregnancy in women with a history of preeclampsia.Pregnancy hypertension · 2026Article
- Aberrant Uteroplacental and Vascular Signaling and Remodeling by Matrix Metalloproteinases in Pregnancy-Related Hypertension and Preeclampsia.Biomolecules · 2026Review
- Maternal Microvascular Dysfunction During and After Preeclamptic Pregnancy.Comprehensive Physiology · 2024Review
- MicroRNA-195-5p Attenuates Pregnancy-Induced Hypertension by Inhibiting Oxidative Stress via OTX1/MAPK Signaling Pathway.Biochemical genetics · 2024Article
- Increased uterine arterial tone, stiffness and remodeling with augmented matrix metalloproteinase-1 and -7 in uteroplacental ischemia-induced hypertensive pregnancy.Biochemical pharmacology · 2024Article
- Regulation of vascular angiotensin II type 1 and type 2 receptor and angiotensin-(1-7)/MasR signaling in normal and hypertensive pregnancy.Biochemical pharmacology · 2024Review
- Gestational intermittent hypoxia induces endothelial dysfunction and hypertension in pregnant rats: role of endothelin type B receptor†.Biology of reproduction · 2024Article
- Increased CaBiochemical pharmacology · 2023Article
- PAD4 silencing inhibits inflammation whilst promoting trophoblast cell invasion and migration by inactivating the NEMO/NF-κB pathway.Experimental and therapeutic medicine · 2022Article
- Chemerin promotes the pathogenesis of preeclampsia by activating CMKLR1/p-Akt/CEBPɑ axis and inducing M1 macrophage polarization.Cell biology and toxicology · 2022Article
- Role of microRNAs in trophoblast invasion and spiral artery remodeling: Implications for preeclampsia.Frontiers in cell and developmental biology · 2022Review
- TNFα blockade reverses vascular and uteroplacental matrix metalloproteinases imbalance and collagen accumulation in hypertensive pregnant rats.Biochemical pharmacology · 2021Article
- Uteroplacental Circulation in Normal Pregnancy and Preeclampsia: Functional Adaptation and Maladaptation.International journal of molecular sciences · 2021Review
- Carbonic anhydrase inhibition improves pulmonary artery reactivity and nitric oxide-mediated relaxation in sugen-hypoxia model of pulmonary hypertension.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Vascular mechanisms and molecular targets in hypertensive pregnancy and preeclampsia.American journal of physiology. Heart and circulatory physiology · 2020Review
- Microvascular Disease and Small-Vessel Disease: The Nexus of Multiple Diseases of Women.Journal of women's health (2002) · 2020Article
- Decreased uterine vascularization and uterine arterial expansive remodeling with reduced matrix metalloproteinase-2 and -9 in hypertensive pregnancy.American journal of physiology. Heart and circulatory physiology · 2020Article
- HIF-1α regulates angiogenesis via Notch1/STAT3/ETBR pathway in trophoblastic cells.Cell cycle (Georgetown, Tex.) · 2019Article
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Abstract
Preeclampsia is a pregnancy-related disorder characterized by hypertension with an unclear mechanism. Studies have shown endothelial dysfunction and increased endothelin-1 (ET-1) levels in hypertensive pregnancy (HTN-Preg). ET-1 activates endothelin receptor type-A in vascular smooth muscle to induce vasoconstriction, but the role of vasodilator endothelial endothelin receptor type-B (ETBR) in the changes in blood pressure (BP) and vascular function in HTN-Preg is unclear. To test whether downregulation of endothelial ETBR expression/activity plays a role in HTN-Preg, BP was measured in normal pregnancy (Norm-Preg) rats and rat model of HTN-Preg produced by reduction of uteroplacental perfusion pressure (RUPP), and mesenteric microvessels were isolated for measuring diameter, [Ca(2+)]i, and endothelin receptor type-A and ETBR levels. BP, ET-1- and potassium chloride-induced vasoconstriction, and [Ca(2+)]i were greater in RUPP than in Norm-Preg rats. Endothelium removal or microvessel treatment with ETBR antagonist BQ-788 enhanced ET-1 vasoconstriction and [Ca(2+)]i in Norm-Preg, but not RUPP, suggesting reduced vasodilator ETBR in HTN-Preg. The ET-1+endothelin receptor type-A antagonist BQ-123 and the ETBR agonists sarafotoxin 6c and IRL-1620 caused less vasorelaxation and nitrate/nitrite production in RUPP than in Norm-Preg. The nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester reduced sarafotoxin 6c- and IRL-1620-induced relaxation in Norm-Preg but not in RUPP, supporting that ETBR-mediated nitric oxide pathway is compromised in RUPP. Reverse transcription polymerase chain reaction, Western blots, and immunohistochemistry revealed reduced endothelial ETBR expression in RUPP. Infusion of BQ-788 increased BP in Norm-Preg, and infusion of IRL-1620 reduced BP and ET-1 vasoconstriction and [Ca(2+)]i and enhanced ETBR-mediated vasorelaxation in RUPP. Thus, downregulation of microvascular vasodilator ETBR is a central mechanism in HTN-Preg, and increasing ETBR activity could be a target in managing preeclampsia.
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