Document Detail

Renal salt wasting in mice lacking NHE3 Na+/H+ exchanger but not in mice lacking NHE2.
MedLine Citation:
PMID:  11553519     Owner:  NLM     Status:  MEDLINE    
To study the role of Na+/H+ exchanger isoform 2 (NHE2) and isoform 3 (NHE3) in sodium-fluid volume homeostasis and renal Na+ conservation, mice with Nhe2 (Nhe2-/-) and/or Nhe3 (Nhe3-/-) null mutations were fed a Na+-restricted diet, and urinary Na+ excretion, blood pressure, systemic acid-base and electrolyte status, and renal function were analyzed. Na+ -restricted Nhe2-/- mice, on either a wild-type or Nhe3 heterozygous mutant (Nhe3+/-) background, did not exhibit excess urinary Na+ excretion. After 15 days of Na+ restriction, blood pressure, fractional excretion of Na+, and the glomerular filtration rate (GFR) of Nhe2-/-Nhe3+/- mice were similar to those of Nhe2+/+ and Nhe3+/- mice, and no metabolic disturbances were observed. Nhe3-/- mice maintained on a Na+-restricted diet for 3 days exhibited hyperkalemia, urinary salt wasting, acidosis, sharply reduced blood pressure and GFR, and evidence of hypovolemic shock. These results negate the hypothesis that NHE2 plays an important renal function in sodium-fluid volume homeostasis; however, they demonstrate that NHE3 is critical for systemic electrolyte, acid-base, and fluid volume homeostasis during dietary Na+ restriction and that its absence leads to renal salt wasting.
C Ledoussal; J N Lorenz; M L Nieman; M Soleimani; P J Schultheis; G E Shull
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  281     ISSN:  1931-857X     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2001-09-12     Completed Date:  2001-10-11     Revised Date:  2011-04-28    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F718-27     Citation Subset:  IM    
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, USA.
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MeSH Terms
Acid-Base Equilibrium / physiology
Blood Pressure
Diet, Sodium-Restricted
Drinking / physiology
Feces / chemistry
Glomerular Filtration Rate / physiology
Kidney / physiology*
Mice, Mutant Strains
Potassium / analysis,  urine
Sodium, Dietary / analysis,  pharmacokinetics*,  urine
Sodium-Hydrogen Antiporter / genetics*,  metabolism*
Water-Electrolyte Balance / physiology*
Grant Support
Reg. No./Substance:
0/Slc9a2 protein, mouse; 0/Sodium, Dietary; 0/Sodium-Hydrogen Antiporter; 0/sodium-hydrogen exchanger 3; 7440-09-7/Potassium

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