Renal tubular NHE3 is required in the maintenance of water and sodium chloride homeostasis

Kidney Int. 2017 Aug;92(2):397-414. doi: 10.1016/j.kint.2017.02.001. Epub 2017 Apr 3.

Abstract

The sodium/proton exchanger isoform 3 (NHE3) is expressed in the intestine and the kidney, where it facilitates sodium (re)absorption and proton secretion. The importance of NHE3 in the kidney for sodium chloride homeostasis, relative to the intestine, is unknown. Constitutive tubule-specific NHE3 knockout mice (NHE3loxloxCre) did not show significant differences compared to control mice in body weight, blood pH or bicarbonate and plasma sodium, potassium, or aldosterone levels. Fluid intake, urinary flow rate, urinary sodium/creatinine, and pH were significantly elevated in NHE3loxloxCre mice, while urine osmolality and GFR were significantly lower. Water deprivation revealed a small urinary concentrating defect in NHE3loxloxCre mice on a control diet, exaggerated on low sodium chloride. Ten days of low or high sodium chloride diet did not affect plasma sodium in control mice; however, NHE3loxloxCre mice were susceptible to low sodium chloride (about -4 mM) or high sodium chloride intake (about +2 mM) versus baseline, effects without differences in plasma aldosterone between groups. Blood pressure was significantly lower in NHE3loxloxCre mice and was sodium chloride sensitive. In control mice, the expression of the sodium/phosphate co-transporter Npt2c was sodium chloride sensitive. However, lack of tubular NHE3 blunted Npt2c expression. Alterations in the abundances of sodium/chloride cotransporter and its phosphorylation at threonine 58 as well as the abundances of the α-subunit of the epithelial sodium channel, and its cleaved form, were also apparent in NHE3loxloxCre mice. Thus, renal NHE3 is required to maintain blood pressure and steady-state plasma sodium levels when dietary sodium chloride intake is modified.

Keywords: aldosterone; distal tubule; hypernatremia; hyponatremia; proximal tubule.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood Pressure*
  • Epithelial Sodium Channels / metabolism
  • Heart Rate
  • Homeostasis*
  • Kidney Tubules / metabolism*
  • Mice, Knockout
  • Sodium Chloride Symporters / metabolism
  • Sodium Chloride, Dietary / metabolism*
  • Sodium-Hydrogen Exchanger 3 / metabolism*

Substances

  • Epithelial Sodium Channels
  • Slc9a3 protein, mouse
  • Sodium Chloride Symporters
  • Sodium Chloride, Dietary
  • Sodium-Hydrogen Exchanger 3