Kidney Week

Abstract: SA-PO1011

Sexual Dimorphic Responses of Renal Transporters to High Salt Diet Favor More Diuresis in Females

Session Information

• Fluid and Electrolytes: Basic - II
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid and Electrolytes

• 901 Fluid and Electrolytes: Basic

Authors

• Torres, Diana L., Keck School of Medicine of USC, Los Angeles, California, United States

Diana L. Torres,

• Veiras, Luciana C., Keck School of Medicine of USC, Los Angeles, California, United States

Luciana C. Veiras,

• Ralph, Donna, Keck School of Medicine of USC, Los Angeles, California, United States

Donna Ralph,

• Khalil, Zoya, Keck School of Medicine of USC, Los Angeles, California, United States

Zoya Khalil,

• Lisboa, Hector R., Keck School of Medicine of USC, Los Angeles, California, United States

Hector R. Lisboa,

• McDonough, Alicia A., Keck School of Medicine of USC, Los Angeles, California, United States

Alicia A. McDonough,

Background

Previous studies have shown that there are distinct sexual dimorphic patterns of transporters along the nephron. Compared to males (M), female (F) rats and mice at baseline have less proximal tubule sodium transporters (NHE3, NaPi2) and more activated distal NCC and collecting duct epithelial sodium channels (ENaC). Also, F are reported to have a have more robust pressure natriuretic response than M. This study aimed to test the hypothesis that, in F vs. M C57Bl/6 mice, high salt diet regulates renal Na⁺ transporters, claudins (Cld) and the regulatory kinase (SPAK) in a pattern that facilitates more natriuresis in females.

Methods

For 2 wk, mice (n=7/group) received a normal salt diet (0.26% NaCl, NSD) or a high salt diet (4.0% NaCl, HSD). Urine Na⁺ and K⁺ were measured by flame photometry and osmolality with an osmometer. Renal transporter and channel abundance was determined by quantitative immunoblot, and subcellular distribution by confocal immunohistochemistry.

Results

At baseline, F exhibit lower urinary volume (UV), Na⁺ (UNaV), K⁺ (UKV), and osmoles (UosmV); F also had lower abundance of the PT NHE3, NHE3p and Cld2 and higher DCT NCC and SPAK compared to M. In response to HSD, F vs. M exhibit greater fold increases in UV (5- vs. 1.6-fold), UNaV (25- vs. 8-fold), UKV (2.3-fold vs. no increase) and UosmV (6 vs. 2-fold) and no change in plasma [Na⁺] or [K⁺]. During HSD NHE3p, a marker for less activity, increased in M but not F. During HSD, abundance of NKCCp, NCCp, and cleaved ENaC alpha decreased in both sexes, evidence of less activity of these transporters from loop through collecting duct. SPAK and Cld7 were unchanged. At baseline, NHE3 and NHE3p were located in the villi in M and at the base of the villi in F; with HSD NHE3, NHE3p redistributed to the villar base in M and were unchanged in F. NCCp remained localized to the apical membranes in both sexes.

Conclusion

The renal responses to a high salt diet are sex dependent: redistribution of NHE3 and NHE3p in males, and reduced NKCC2p, NCC, NCCp and α ENaC cleavage in both sexes contribute to natriuresis. Females exhibit more robust natriuresis and diuresis during HSD which we hypothesize is due, at least in part, to the lower baseline PT NHE3 and Cld2.

Funding

• NIDDK Support