Abstract: TH-PO1018

Sex Differences in Renal Ammonia Metabolism

Session Information

  • Acid Base: Basic
    November 02, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Fluid, Electrolytes, and Acid-Base

  • 701 Acid-Base: Basic

Authors

  • Harris, Autumn N, University of Florida , Gainesville, Florida, United States
  • Osis, Gunars, University of Florida , Gainesville, Florida, United States
  • Lee, Hyun-Wook, University of Florida , Gainesville, Florida, United States
  • Webster, Kierstin L, University of Florida , Gainesville, Florida, United States
  • Verlander, Jill W., University of Florida , Gainesville, Florida, United States
  • Weiner, I. David, University of Florida , Gainesville, Florida, United States
Background

Renal ammonia excretion is an important component of acid-base homeostasis. Previous studies indicate that sex impacts multiple aspects of renal function. This study’s purpose was to investigate gender differences in renal ammonia metabolism.

Methods

We compared 4-month-old male (M) and female (F) C57Bl/6 mice, with measurement of plasma electrolytes, urinary ammonia excretion, and evaluation of changes in key proteins involved in ammonia metabolism using immunoblot analysis and immunohistochemistry.

Results

Under basal conditions, female mice excreted significantly more urine ammonia than male mice (F, 71.9±22.9; M, 46.1±18.6 µmol/day; P ≤ 0.02) and had significantly lower plasma bicarbonate concentrations than male mice (F, 18.1±1.6; M, 19.9±1.5 mmol/L; P ≤ 0.02). Titratable acid excretion (F, 63±42; M, 78±17 µmol/day), urine pH (F, 6.40±0.18; M, 6.36±0.14), plasma Na+ and K+ concentrations, and food intake (F, 8.9±0.9; M, 9.6±1.2 g/day) did not differ significantly. Total expression of key ammonia generating proteins, phosphoenolypyruvate and phosphate-dependent glutaminase were significantly greater in the cortex of female than male mice. Expression of glutamine synthetase, which recycles ammonia, was significantly greater in the cortical proximal tubules (PT) of female mice. Expression of NBCe1, a basolateral PT bicarbonate transporter, recently shown to regulate PT ammonia metabolism, did not differ significantly between sexes. Expression of the ammonia transporter family member, Rhbg, was significantly greater in connecting segment cells and intercalated and principal cells in the collecting duct in the cortex and inner stripe of the outer medulla (ISOM) in female mice. Expression of Rhcg was significantly greater in female mice in connecting segment cells and in the basolateral membrane of intercalated and principal cells in the collecting duct in the ISOM.

Conclusion

Despite similar levels of food intake and thus protein intake, which is the primary determinant of endogenous acid production, female mice excreted higher amounts of basal ammonia, but not titratable acid. This increase in ammonia excretion was associated with differences in the expression of several proteins involved in ammonia generation and transport. Thus, there are sex-dependent differences in basal ammonia metabolism and acid-base homeostasis.

Funding

  • NIDDK Support