Microsomal Prostaglandin Synthase-1-Derived Prostaglandin E-2 Protects Against Angiotensin II-Induced Hypertension via Inhibition of Oxidative Stress

作者：Jia Zhanjun; Guo Xiaohua; Zhang Hui; Wang Mong Heng; Dong Zheng; Yang Tianxin^*

来源：Hypertension, 2008, 52(5): 952-U573.

DOI：10.1161/HYPERTENSIONAHA.108.111229

• mPGES-1
• angiotensin II
• mean arterial pressure
• oxidative stress
• NADPH oxidase

Prostaglandin (PG) E-2 has an established role in the regulation of vascular tone and reactivity. The present study examined the role and mechanism of microsomal PG synthase-1 (mPGES-1) in vascular response to angiotensin II (Ang II) infusion. A 7-day Ang II infusion at 0.35 mg/kg per day via osmotic minipump had no obvious effect on mean arterial blood pressure in mPGES-1(+/+) mice but induced a marked hypertensive response in mPGES-1(-/-) mice, associated with a parallel increase in urinary 8-isoprostane excretion and aortic NADPH oxidase activity and mRNA expression of p47(phox), gp91(phox), and Nox1. The hypertension in mPGES-1(-/-) mice was completely prevented by Tempol treatment and was fully restored on termination of the antioxidant. Apocynin induced a similar blood pressure-lowering effect as Tempol. The Ang II infusion induced mRNA expression of mPGES-1, as well as mPGES-2 and cytosolic PGE synthase in the aortas as assessed by real-time RT-PCR. Immunohistochemistry revealed remarkably enhanced immunoreactivity of mPGES-1 mostly in vascular smooth muscle cells. In cultured vascular smooth muscle cells, Ang II exerted a direct stimulatory effect on reactive oxygen species production, NADPH oxidase activity, and expression of p47(phox), gp91(phox), and Nox1 that were all inhibited by PGE(2). The(-/-) mice also exhibited enhanced renal hemodynamic response to acute Ang II infusion at 150 nmol/kg per minute via a jugular vein over a period of 40 minutes. These results suggest that mPGES-1-derived PGE(2) buffers Ang II-induced vasoconstriction via inhibition of NADPH oxidase-dependent reactive oxygen species production. (Hypertension. 2008;52:952-959.)

• 出版日期2008-11