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Publication
Inactivation of the E-prostanoid 3 receptor attenuates the angiotensin II
pressor response via decreasing arterial contractility.
Authors Chen L, Miao Y, Zhang Y, Dou D, Liu L, Tian X, Yang G, Pu D, Zhang X, Kang J,
Gao Y, Wang S, Breyer MD, Wang N, Zhu Y, Huang Y, Breyer RM, Guan Y
Submitted By Submitted Externally on 7/17/2018
Status Published
Journal Arteriosclerosis, thrombosis, and vascular biology
Year 2012
Date Published 12/1/2012
Volume : Pages 32 : 3024 - 32
PubMed Reference 23065824
Abstract The present studies aimed at elucidating the role of prostaglandin E(2) receptor
subtype 3 (E-prostanoid [EP] 3) in regulating blood pressure., 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., 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.




Strains




Genes
SymbolDescription
Ptger3prostaglandin E receptor 3 (subtype EP3)

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