Inactivation of the E-Prostanoid 3 Receptor Attenuates the Angiotensin II Pressor Response via Decreasing Arterial Contractility

被引：54

作者：

Chen, Lihong ^{[1
,2
]}

Miao, Yifei ^{[1
,2
]}

Zhang, Yahua

Dou, Dou ^{[1
]}

Liu, Limei ^{[1
]}

Tian, Xiaoyu ^{[4
]}

Yang, Guangrui ^{[1
,2
]}

Pu, Dan ^{[1
,2
]}

Zhang, Xiaoyan ^{[1
,2
]}

Kang, Jihong ^{[1
,2
]}

Gao, Yuansheng

Wang, Shigiang ^{[5
]}

Breyer, Matthew D. ^{[3
]}

Wang, Nanping ^{[2
]}

Zhu, Yi ^{[1
,2
,3
]}

Huang, Yu ^{[4
]}

Breyer, Richard M. ^{[3
]}

Guan, Youfei

机构：

[1] Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China

[2] Minist Educ, Key Lab Cardiovasc Sci, Beijing, Peoples R China

[3] Vanderbilt Univ, Med Ctr, Dept Med, Div Nephrol & Hypertens, Nashville, TN USA

[4] Chinese Univ Hong Kong, Sch Biomed Sci, Li Ka Shing Inst Hlth Sci, Inst Vasc Med, Shatin, Hong Kong, Peoples R China

[5] Peking Univ, Inst Life Sci, Beijing 100191, Peoples R China

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 2012年 / 32卷 / 12期

基金：

美国国家卫生研究院;

关键词：

angiotensin II; calcium; E-prostanoid; 3; hypertension; vasoconstriction; C-TERMINAL TAIL; BLOOD-PRESSURE; EP3; RECEPTOR; PROSTAGLANDIN RECEPTORS; MICE LACKING; SUBTYPE; EXPRESSION; HYPERTENSION; ISOFORMS; CALCIUM;

D O I：

10.1161/ATVBAHA.112.254052

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.)

引用

页码：3024 / +

页数：22

共 51 条

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