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 language | English (US) |
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Pages (from-to) | 952-959 |
Number of pages | 8 |
Journal | Hypertension |
Volume | 52 |
Issue number | 5 |
DOIs | |
State | Published - Nov 2008 |
Keywords
- Angiotensin ii
- Mean arterial pressure
- Mpges-1
- Nadph oxidase
- Oxidative stress
ASJC Scopus subject areas
- Internal Medicine