Microsomal Prostaglandin Synthase-1–Derived Prostaglandin E 2 Protects Against Angiotensin II–Induced Hypertension via Inhibition of Oxidative Stress
| Autor: | Tianxin Yang, Zhanjun Jia, Hui Zhang, Mong Heng Wang, Zheng Dong, Xiaohua Guo |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Vascular smooth muscle medicine.medical_treatment Prostaglandin Nitric Oxide Muscle Smooth Vascular Mice chemistry.chemical_compound Internal medicine Internal Medicine medicine Animals Receptors Prostaglandin E NADH NADPH Oxidoreductases Prostaglandin E2 Cells Cultured Prostaglandin-E Synthases Mice Knockout Membrane Glycoproteins NADPH oxidase biology Angiotensin II NADPH Oxidases Receptors Prostaglandin E EP2 Subtype Mice Mutant Strains Intramolecular Oxidoreductases Mice Inbred C57BL Oxidative Stress Endocrinology chemistry Mice Inbred DBA NOX1 Hypertension NADPH Oxidase 2 Apocynin NADPH Oxidase 1 cardiovascular system biology.protein Female lipids (amino acids peptides and proteins) Reactive Oxygen Species Receptors Prostaglandin E EP4 Subtype Signal Transduction medicine.drug Prostaglandin E |
| Zdroj: | Hypertension. 52:952-959 |
| ISSN: | 1524-4563 0194-911X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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