Document Detail


Inactivation of the E-prostanoid 3 receptor attenuates the angiotensin II pressor response via decreasing arterial contractility.
MedLine Citation:
PMID:  23065824     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: The present studies aimed at elucidating the role of prostaglandin E(2) receptor subtype 3 (E-prostanoid [EP] 3) in regulating blood pressure.
METHODS AND RESULTS: Mice bearing a genetic disruption of the EP3 gene (EP(3)(-/-)) exhibited reduced baseline mean arterial pressure monitored by both tail-cuff and carotid arterial catheterization. The pressor responses induced by EP3 agonists M&B28767 and sulprostone were markedly attenuated in EP3(-/-) mice, whereas the reduction of blood pressure induced by prostaglandin E(2) was comparable in both genotypes. Vasopressor effect of acute or chronic infusion of angiotensin II (Ang II) was attenuated in EP3(-/-) mice. Ang II-induced vasoconstriction in mesenteric arteries decreased in EP3(-/-) group. In mesenteric arteries from wild-type mice, Ang II-induced vasoconstriction was inhibited by EP3 selective antagonist DG-041 or L798106. The expression of Arhgef-1 is attenuated in EP3 deficient mesenteric arteries. EP3 antagonist DG-041 diminished Ang II-induced phosphorylation of myosin light chain 20 and myosin phosphatase target subunit 1 in isolated mesenteric arteries. Furthermore, in vascular smooth muscle cells, Ang II-induced intracellular Ca(2+) increase was potentiated by EP3 agonist sulprostone but inhibited by DG-041.
CONCLUSIONS: Activation of the EP3 receptor raises baseline blood pressure and contributes to Ang II-dependent hypertension at least partially via enhancing Ca(2+) sensitivity and intracellular calcium concentration in vascular smooth muscle cells. Selective targeting of the EP3 receptor may represent a potential therapeutic target for the treatment of hypertension.
Authors:
Lihong Chen; Yifei Miao; Yahua Zhang; Dou Dou; Limei Liu; Xiaoyu Tian; Guangrui Yang; Dan Pu; Xiaoyan Zhang; Jihong Kang; Yuansheng Gao; Shiqiang Wang; Matthew D Breyer; Nanping Wang; Yi Zhu; Yu Huang; Richard M Breyer; Youfei Guan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-11
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  32     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-15     Completed Date:  2013-01-29     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3024-32     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II / pharmacology*
Animals
Blood Pressure / drug effects*,  physiology
Calcium / metabolism
Cells, Cultured
Gene Deletion
Guanine Nucleotide Exchange Factors / metabolism
Male
Mesenteric Arteries / drug effects,  physiology*
Mice
Mice, Inbred C57BL
Mice, Knockout
Models, Animal
Muscle, Smooth, Vascular / cytology,  metabolism
Receptors, Prostaglandin E, EP3 Subtype / antagonists & inhibitors*,  genetics*,  physiology
Rho Guanine Nucleotide Exchange Factors
Vasoconstriction / drug effects*,  physiology
Grant Support
ID/Acronym/Agency:
DK46205/DK/NIDDK NIH HHS; I01 BX000616/BX/BLRD VA; P50 GM015431/GM/NIGMS NIH HHS; P50GM015431/GM/NIGMS NIH HHS; R01 DK037097/DK/NIDDK NIH HHS; R01 DK046205/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Arhgef1 protein, mouse; 0/Guanine Nucleotide Exchange Factors; 0/Ptger3 protein, mouse; 0/Receptors, Prostaglandin E, EP3 Subtype; 0/Rho Guanine Nucleotide Exchange Factors; 11128-99-7/Angiotensin II; SY7Q814VUP/Calcium
Comments/Corrections

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


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