Format

Send to

Choose Destination
See comment in PubMed Commons below
Am J Physiol Renal Physiol. 2013 Jan 15;304(2):F214-21. doi: 10.1152/ajprenal.00588.2011. Epub 2012 Nov 21.

mPGES-1-derived PGE2 mediates dehydration natriuresis.

Author information

1
Univ. of Utah and Veterans Affairs Medical Center, Div. of Nephrology and Hypertension, Salt Lake City, UT 84132, USA.

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.

PMID:
23171554
PMCID:
PMC3543622
DOI:
10.1152/ajprenal.00588.2011
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments

    Supplemental Content

    Full text links

    Icon for Atypon Icon for PubMed Central
    Loading ...
    Support Center