| Deletion of G protein-coupled estrogen receptor increases endothelial vasoconstriction. | |
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MedLine Citation:
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PMID: 22203741 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Endogenous estrogens mediate protective effects in the cardiovascular system, affecting both endothelium-dependent and endothelium-independent mechanisms. Previous studies have suggested that nonselective estrogen receptor agonists such as endogenous estrogens inhibit endothelium-dependent vasoconstriction; however, the role of estrogen receptors in this response has not yet been clarified. This study investigated whether the intracellular transmembrane G protein-coupled estrogen receptor (GPER) regulates vascular reactivity in mice. Effects of chronic deficiency (using mice lacking the GPER gene) and acute inhibition (using the GPER-selective antagonist G15) on endothelium-dependent and endothelium-independent vascular reactivity, and the effects of GPER deficiency on vascular gene expression and structure were investigated. We found that chronic GPER deficiency is associated with increased endothelial prostanoid-mediated vasoconstriction but has no effect on endothelial nitric oxide bioactivity, gene expression of endothelial nitric oxide synthase and thromboxane prostanoid (TP) receptor, or vascular structure. GPER deletion also increases TP receptor-mediated contraction. Acute GPER blockade enhances endothelium-dependent contractions and reduces endothelial nitric oxide bioactivity. Contractions in response to TP receptor activation are unaffected by G15. In conclusion, this study identifies GPER as the first estrogen receptor with inhibitory activity on endothelium-dependent contractility. These findings may be important for understanding and treating diseases associated with increased endothelial vasoconstrictor prostanoid activity such as hypertension and obesity. |
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Authors:
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Matthias R Meyer; Kerstin Amann; Angela S Field; Chelin Hu; Helen J Hathaway; Nancy L Kanagy; Mary K Walker; Matthias Barton; Eric R Prossnitz |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-12-27 |
Journal Detail:
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Title: Hypertension Volume: 59 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-01-25 Completed Date: 2012-04-20 Revised Date: 2013-04-08 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 507-12 Citation Subset: IM |
Affiliation:
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Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Benzodioxoles / pharmacology Disease Models, Animal Endothelium, Vascular / metabolism, physiopathology* Gene Deletion* Male Mice Mice, Knockout Nitric Oxide / metabolism Nitric Oxide Synthase Type III / metabolism Quinolines / pharmacology Receptors, G-Protein-Coupled / antagonists & inhibitors, deficiency*, genetics* Receptors, Thromboxane / metabolism Vasoconstriction / drug effects, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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CA127731/CA/NCI NIH HHS; HL078914/HL/NHLBI NIH HHS; HL82799/HL/NHLBI NIH HHS; R01 CA127731/CA/NCI NIH HHS; R01 CA127731-04/CA/NCI NIH HHS; R01 CA127731-05/CA/NCI NIH HHS; UL1 TR000041/TR/NCATS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H-cyclopenta(c)quinoline; 0/Benzodioxoles; 0/Quinolines; 0/Receptors, G-Protein-Coupled; 0/Receptors, Thromboxane; 10102-43-9/Nitric Oxide; EC 1.14.13.39/Nitric Oxide Synthase Type III |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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