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Acta Pharmacol. Sin. · Oct 2010
Enhanced pressor response to acute Ang II infusion in mice lacking membrane-associated prostaglandin E2 synthase-1.
- Dong-juan Zhang, Li-hong Chen, Ya-hua Zhang, Guang-rui Yang, Dou Dou, Yuan-sheng Gao, Xiao-yan Zhang, Xiao-mu Kong, Pan Zhao, Dan Pu, Ming-fen Wei, Matthew-D Breyer, and You-fei Guan.
- Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China.
- Acta Pharmacol. Sin. 2010 Oct 1; 31 (10): 1284-92.
AimTo examine the contribution of vascular membrane-associated prostaglandin E2 synthase-1 (mPGES-1) to acute blood pressure homeostasis.MethodsAngiotensin II (AngII, 75 pmol·kg⁻¹·min⁻¹) was continuously infused via the jugular vein into wild-type and mPGES-1(-/-) mice for 30 min, and blood pressure was measured by carotid arterial catheterization. RT-PCR and immunohistochemistry were performed to detect the expression and localization of mPGES-1 in the mouse arterial vessels. Mesenteric arteries were dissected from mice of both genotypes to study vessel tension and measure vascular PGE2 levels.ResultsWild-type and mPGES-1(-/-) mice showed similar blood pressure levels at baseline, and the acute intravenous infusion of AngII caused a greater increase in mean arterial pressure in the mPGES-1(-/-) group, with a similar diuretic and natriuretic response in both groups. mPGES-1 was constitutively expressed in the aortic and mesenteric arteries and vascular smooth muscle cells of wild-type mice. Strong staining was detected in the smooth muscle layer of arterial vessels. Ex vivo treatment of mesenteric arteries with AngII produced more vasodilatory PGE2 in wild-type than in mPGES-1(-/-) mice. In vitro tension assays further revealed that the mesenteric arteries of mPGES-1(-/-) mice exhibited a greater vasopressor response to AngII than those arteries of wild-type mice.ConclusionVascular mPGES-1 acts as an important tonic vasodilator, contributing to acute blood pressure regulation.
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