mPGES-1 deletion impairs diuretic response to acute water loading.
PGE(2) 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 PGE(2) excretion in the +/+ mice increased at 2 h, in parallel with increased urine flow. In contrast, the -/- mice exhibited a delayed increase in urinary PGE(2) 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.
Soodvilai
Sunhapas
S
Department of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah, USA.
Jia
Zhanjun
Z
Wang
Mong-Heng
MH
Dong
Zheng
Z
Yang
Tianxin
T
D000208:Acute Disease; D000818:Animals; D051399:Aquaporin 2 / Q000235:genetics / Q000378:metabolism; D002908:Chronic Disease; D015232:Dinoprostone / Q000378:metabolism; D004231:Diuresis / Q000502:physiology*; D004326:Drinking / Q000502:physiology*; D017353:Gene Deletion; D019746:Intramolecular Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D007679:Kidney Medulla / Q000502:physiology; D007685:Kidney Tubules, Collecting / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D000071876:Prostaglandin-E Synthases; D012333:RNA, Messenger / Q000378:metabolism; D014883:Water-Electrolyte Imbalance / Q000378:metabolism / Q000503:physiopathology*
C496024:Aqp2 protein, mouse; D051399:Aquaporin 2; D012333:RNA, Messenger; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; C000605866:Ptges2 protein, mouse; D015232:Dinoprostone