Microsomal prostaglandin synthase-1-derived prostaglandin E2 protects against angiotensin II-induced hypertension via inhibition of oxidative stress

Zhanjun Jia, Xiaohua Guo, Hui Zhang, Mong-Heng Wang, Zheng Dong, Tianxin Yang

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Prostaglandin (PG) E2 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 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 p47phox, gp91phox, 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 p47phox, gp91phox. and Nox1 that were all inhibited by PGE2. 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 PGE2 buffers Ang 11-induced vasoconstriction via inhibition of NADPH oxidase-dependent reactive oxygen species production.

Original languageEnglish (US)
Pages (from-to)952-959
Number of pages8
JournalHypertension
Volume52
Issue number5
DOIs
StatePublished - Nov 2008

Keywords

  • Angiotensin ii
  • Mean arterial pressure
  • Mpges-1
  • Nadph oxidase
  • Oxidative stress

ASJC Scopus subject areas

  • Internal Medicine

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