mPGES-1 deletion impairs diuretic response to acute water loading

PGE₂ has an established role in renal water handling. The present study was undertaken to examine the role of microsomal prostaglandin E synthase-1 (mPGES-1) in the diuretic response to acute and chronic water loading. Compared with wild-type (+/+) controls, mPGES-1 -/- mice exhibited impaired ability to excrete an acute, but not chronic water load. In response to acute water loading, urinary PGE₂ excretion in the +/+ mice increased at 2 h, in parallel with increased urine flow. In contrast, the -/- mice exhibited a delayed increase in urinary PGE₂ excretion, coinciding with the stimulation of renal medullary mRNA expression of cytosolic prostaglandin E synthase but not mPGES-2. At baseline, renal aquaporin-2 (AQP2) expression in mPGES-1 -/- mice was enhanced compared with the +/+ control. In response to acute water loading, renal AQP2 expression in the +/+ mice was significantly reduced, and this reduction was blunted in the -/- mice. Despite striking changes in AQP2 protein expression, renal AQP2 mRNA in both genotypes largely remained unchanged. Overall, these data support an important role of mPGES-1 in provoking the diuretic response to acute water loading.