title: mPGES-1-derived PGE2 mediates dehydration natriuresis.
abstract: PGE(2) is a natriuretic factor whose production is elevated after water deprivation (WD) but its role in dehydration natriuresis is not well-defined. The goal of the present study was to investigate the role of microsomal prostaglandin E synthase-1 (mPGES-1) in dehydration natriuresis. After 24-h WD, wild-type (WT) mice exhibited a significant increase in 24-h urinary Na(+) excretion accompanied with normal plasma Na(+) concentration and osmolality. In contrast, WD-induced elevation of urinary Na(+) excretion was completely abolished in mPGES-1 knockout (KO) mice in parallel with increased plasma Na(+) concentration and a trend increase in plasma osmolality. WD induced a 1.8-fold increase in urinary PGE(2) output and a 1.6-fold increase in PGE(2) content in the renal medulla of WT mice, both of which were completely abolished by mPGES-1 deletion. Similar patterns of changes were observed for urinary nitrate/nitrite and cGMP. The natriuresis in dehydrated WT mice was associated with a significant downregulation of renal medullary epithelial Na channel-α mRNA and protein, contrasting to unaltered expressions in dehydrated KO mice. By quantitative RT-PCR, WD increased the endothelial nitric oxide synthase (eNOS), inducible NOS, and neuronal NOS expressions in the renal medulla of WT mice by 3.9-, 1.48-, and 2.6-fold, respectively, all of which were significantly blocked in mPGES-1 KO mice. The regulation of eNOS expression was further confirmed by immunoblotting. Taken together, our results suggest that mPGES-1-derived PGE(2) contributes to dehydration natriuresis likely via NO/cGMP.
authors.affiliation: Univ. of Utah and Veterans Affairs Medical Center, Div. of Nephrology and Hypertension, Salt Lake City, UT 84132, USA.
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Jia
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kakizoe
authors.forename: Guangju
authors.initials: G
authors.lastname: Guan
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhang
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Zhou
authors.forename: Tianxin
authors.initials: T
authors.lastname: Yang
mesh_terms: D000818:Animals; D003681:Dehydration / Q000378:metabolism*; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009318:Natriuresis / Q000502:physiology*; D010949:Plasma / Q000737:chemistry; D000071876:Prostaglandin-E Synthases; D012964:Sodium / Q000097:blood / Q000378:metabolism; D014867:Water / Q000378:metabolism; D014868:Water Deprivation; D014883:Water-Electrolyte Imbalance
chemical_list: D014867:Water; D012964:Sodium; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; D015232:Dinoprostone