Sexual Dimorphic Pattern of Renal Transporters and Electrolyte Homeostasis

Author(s):Show less -

Veiras, Luciana C. ^[1] ; Girardi, Adriana C. C. ^[2] ; Curry, Joshua ^[3] ; Pei, Lei ^[3] ; Ralph, Donna L. ^[1] ; Tran, An ; Castelo-Branco, Regiane C. ^[4] ; Pastor-Soler, Nuria ^[5] ; Arranz, Cristina T. ^[6] ; Yu, Alan S. L. ^[3] ; McDonough, Alicia A. ^[7]

Affiliation

^[1] Univ Southern Calif, Keck Sch Med, Dept Integrat Anat Sci, Los Angeles, CA - USA

^[2] Univ Sao Paulo, Med Sch, Heart Inst, Sao Paulo - Brazil

^[3] Univ Kansas, Med Ctr, Kidney Inst, Kansas City, KS 66103 - USA

^[4] Univ Sao Paulo, Biomed Sci Inst, Dept Physiol & Biophys, Sao Paulo - Brazil

^[5] Univ Southern Calif, Keck Sch Med, Dept Med, Div Nephrol & Hypertens, Los Angeles, CA 90033 - USA

^[6] Univ Buenos Aires, Natl Council Sci & Technol, Buenos Aires, DF - Argentina

^[7] An Tran, Univ Southern Calif, Keck Sch Med, Dept Integrat Anat Sci, Los Angeles, CA - USA

• Document type: Journal article
• Source: JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY; v. 28, n. 12, p. 3504-3517, DEC 2017.
• Web of Science Citations: 43

Abstract

Compared with males, females have lower BP before age 60, blunted hypertensive response to angiotensin II, and a leftward shift in pressure natriuresis. This study tested the concept that this female advantage associates with a distinct sexual dimorphic pattern of transporters along the nephron. We applied quantitative immunoblotting to generate profiles of transporters, channels, claudins, and selected regulators in both sexes and assessed the physiologic consequences of the differences. In rats, females excreted a saline load more rapidly than males did. Compared with the proximal tubule of males, the proximal tubule of females had greater phosphorylation of Na+/H+ exchanger isoform 3 (NHE3), distribution of NHE3 at the base of the microvilli, and less abundant expression of Na+/Pi cotransporter 2, claudin-2, and aquaporin 1. These changes associated with less bicarbonate reabsorption and higher lithium clearance in females. The distal nephrons of females had a higher abundance of total and phosphorylated Na+/Cl- cotransporter (NCC), claudin-7, and cleaved forms of epithelial Na+ channel (ENaC) alpha and gamma subunits, which associated with a lower baseline plasma K+ concentration. A K+-rich meal increased the urinary K+ concentration and decreased the level of renal phosphorylated NCC in females. Notably, we observed similar abundance profiles in female versus male C57BL/6 mice. These results define sexual dimorphic phenotypes along the nephron and suggest that lower proximal reabsorption in female rats expedites excretion of a saline load and enhances NCC and ENaC abundance and activation, which may facilitate K+ secretion and set plasma K+ at a lower level. (AU)

• FAPESP's process: 12/10146-0 - Molecular mechanisms of regulation of the proximal tubular function in hypertension
• Grantee: Adriana Castello Costa Girardi
• Support Opportunities: Regular Research Grants