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.