Document Detail


Deletion of G protein-coupled estrogen receptor increases endothelial vasoconstriction.
MedLine Citation:
PMID:  22203741     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-12-27
Journal Detail:
Title:  Hypertension     Volume:  59     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-25     Completed Date:  2012-04-20     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  507-12     Citation Subset:  IM    
Affiliation:
Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
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:
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

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