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mPGES-1 protects against DOCA-salt hypertension via inhibition of oxidative stress or stimulation of NO/cGMP.

Abstract
Microsomal prostaglandin E synthase-1 (mPGES-1) is a recently characterized cytokine-inducible enzyme critically involved in pain and inflammatory response. However, its role in blood pressure regulation is still debatable. The present study was undertaken to examine the effect of mPGES-1 deletion on DOCA-salt hypertension. After 2 weeks of DOCA plus 1% NaCl as drinking fluid, hypertension and sodium retention were more severe in mPGES-1 knockout (KO) mice than in wild-type (WT) controls. The indices of oxidative stress including urinary 8-isprostane and renal thiobarbituric acid-reactive substances were only modestly increased or unchanged in the WT mice but more significantly increased in the KO mice after DOCA-salt. Conversely, in response to DOCA-salt, the indices of antioxidant systems including renal expression of superoxide dismutase-3 and urinary nitrate/nitrite excretion were all significantly elevated in the WT mice but remarkably suppressed in the KO mice. Tempol treatment (50 mg/kg per day) in DOCA-salt KO mice produced a marked attenuation of hypertension, sodium retention, and kidney injury. Immunoblotting demonstrated increased renal expression of mPGES-1 in DOCA-salt WT mice. DOCA-salt induced a nearly 5-fold increase in urinary PGE(2) excretion in the WT mice, and this increase was completely abolished in the KO mice. Together, these results suggest that mPGES-1-derived PGE(2) confers protection against DOCA-salt hypertension likely via inhibition of oxidative stress or stimulation of superoxide dismutase-3 and urinary nitrate/nitrite system.
AuthorsZhanjun Jia, Toshinori Aoyagi, Tianxin Yang
JournalHypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 55 Issue 2 Pg. 539-46 (Feb 2010) ISSN: 1524-4563 [Electronic] United States
PMID20065149 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Reactive Oxygen Species
  • Desoxycorticosterone
  • RNA
  • Sodium
  • Nitric Oxide Synthase
  • Superoxide Dismutase
  • Intramolecular Oxidoreductases
  • Prostaglandin-E Synthases
  • Ptges protein, mouse
  • Cyclic GMP
Topics
  • Analysis of Variance
  • Animals
  • Blood Pressure Determination
  • Cyclic GMP (metabolism)
  • Desoxycorticosterone
  • Disease Models, Animal
  • Hypertension (chemically induced, enzymology)
  • Immunoenzyme Techniques
  • Intramolecular Oxidoreductases (metabolism)
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Nitric Oxide Synthase (metabolism)
  • Oxidative Stress (physiology)
  • Prostaglandin-E Synthases
  • RNA (analysis)
  • Random Allocation
  • Reactive Oxygen Species (metabolism)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sodium (metabolism)
  • Superoxide Dismutase (metabolism)
  • Water-Electrolyte Balance (physiology)

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