Document Detail


EP1 disruption attenuates end-organ damage in a mouse model of hypertension.
MedLine Citation:
PMID:  23006735     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Prostaglandin E(2) is a major prostanoid found in the kidney and vasculature contributing to the regulation of blood pressure. The prostaglandin E(2) receptor EP1 has been shown to contribute to hypertension by mediating angiotensin II-dependent vasoconstriction, although its precise role is incompletely characterized. Disruption of the EP1 receptor in C57BL/6J mice reduced the incidence of mortality during severe hypertension induced by uninephrectomy, deoxycorticosterone acetate, and angiotensin II. Mortality was dependent on all components of the model. Death was a result of aortic aneurysm rupture or occurred after development of anasarca, each of which was reduced in EP1-/- mice. Mean arterial pressure was increased in treated EP1+/+ and EP1-/- mice; however, this elevation was significantly lower in EP1-/- mice. Blood pressure reduction via administration of hydralazine phenocopied EP1-/- mice. Thus, reduction in blood pressure by disruption of EP1 reduced incidence of mortality and decreased organ damage, suggesting that EP1 receptor blockade may be a viable target for antihypertensive therapy.
Authors:
Christina S Bartlett; Kelli L Boyd; Raymond C Harris; Roy Zent; Richard M Breyer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-09-24
Journal Detail:
Title:  Hypertension     Volume:  60     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-18     Completed Date:  2013-01-10     Revised Date:  2013-12-31    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1184-91     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II
Animals
Antihypertensive Agents / pharmacology
Aortic Aneurysm / genetics*,  physiopathology
Blood Pressure / drug effects,  genetics,  physiology
Desoxycorticosterone
Disease Models, Animal*
Female
Humans
Hydralazine / pharmacology
Hypertension / etiology,  genetics*,  physiopathology
Kaplan-Meier Estimate
Kidney / metabolism,  pathology,  physiopathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Nephrectomy
Receptors, Prostaglandin E, EP1 Subtype / deficiency,  genetics*
Grant Support
ID/Acronym/Agency:
2P01DK065123/DK/NIDDK NIH HHS; DK059637/DK/NIDDK NIH HHS; DK075594/DK/NIDDK NIH HHS; DK37097/DK/NIDDK NIH HHS; DK46205/DK/NIDDK NIH HHS; DK62794/DK/NIDDK NIH HHS; DK9921/DK/NIDDK NIH HHS; P01 DK065123/DK/NIDDK NIH HHS; P30 DK079341/DK/NIDDK NIH HHS; P30DK79341-01/DK/NIDDK NIH HHS; P50 GM015431/GM/NIGMS NIH HHS; P50GM015431/GM/NIGMS NIH HHS; R01 DK037097/DK/NIDDK NIH HHS; R01 DK046205/DK/NIDDK NIH HHS; R01 DK051265/DK/NIDDK NIH HHS; R01 DK062794/DK/NIDDK NIH HHS; R01 DK075594/DK/NIDDK NIH HHS; U24 DK059637/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Ptger1 protein, mouse; 0/Receptors, Prostaglandin E, EP1 Subtype; 11128-99-7/Angiotensin II; 26NAK24LS8/Hydralazine; 40GP35YQ49/Desoxycorticosterone
Comments/Corrections
Erratum In:
Hypertension. 2013 Dec;62(6):e48

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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