期刊
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
卷 32, 期 12, 页码 3024-+出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.112.254052
关键词
angiotensin II; calcium; E-prostanoid 3; hypertension; vasoconstriction
资金
- Ministry of Science and Technology [2010CB517504, 2010CB912503]
- Natural Science Foundation [30870905/81030003/81121061]
- National Institutes of Health [DK46205, P50GM015431]
Objective-The present studies aimed a 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 (EP3-/-) 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 acme 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 Ca2+ increase was potentiated by EP3 agonist sulprostone but inhibited by DG-041. Conclusion-Activation of the EP3 receptor raises baseline blood pressure and contributes to Ang II dependent hypertension a least partially via enhancing Ca2+ 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. (Arterioscler Thromb Vasc Biol. 2012;32:3024-3032.)
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