title: Renal salt wasting in mice lacking NHE3 Na+/H+ exchanger but not in mice lacking NHE2.
abstract: 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.
authors.affiliation: Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, USA.
authors.forename: C
authors.initials: C
authors.lastname: Ledoussal
authors.forename: J N
authors.initials: JN
authors.lastname: Lorenz
authors.forename: M L
authors.initials: ML
authors.lastname: Nieman
authors.forename: M
authors.initials: M
authors.lastname: Soleimani
authors.forename: P J
authors.initials: PJ
authors.lastname: Schultheis
authors.forename: G E
authors.initials: GE
authors.lastname: Shull
mesh_terms: D000136:Acid-Base Equilibrium / Q000502:physiology; D000818:Animals; D001794:Blood Pressure; D004039:Diet, Sodium-Restricted; D004326:Drinking / Q000502:physiology; D005243:Feces / Q000737:chemistry; D005919:Glomerular Filtration Rate / Q000502:physiology; D007668:Kidney / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D011188:Potassium / Q000032:analysis / Q000652:urine; D012982:Sodium, Dietary / Q000032:analysis / Q000493:pharmacokinetics* / Q000652:urine; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics* / Q000378:metabolism*; D014556:Urine; D014882:Water-Electrolyte Balance / Q000502:physiology*
chemical_list: C513111:Slc9a2 protein, mouse; C000613386:Slc9a3 protein, mouse; D012982:Sodium, Dietary; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D011188:Potassium