ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: SA-PO1048

High K Intake Modulates Thiazide Sensitive Na-Cl Cotransporter Mediated Na and K Transport: Effects of Gender and Angiotensin II Type 1a (AT1a) Receptor

Session Information

  • Na+, K+, Cl-
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Fluid, Electrolytes, and Acid-Base

  • 703 Na+, K+, Cl- Basic

Authors

  • Li, Jing, Yale University, New Haven, Connecticut, United States
  • Xu, Shuhua, Yale University, New Haven, Connecticut, United States
  • Wang, Claire J, Yale University, New Haven, Connecticut, United States
  • Hu, Haiyan, Yale University, New Haven, Connecticut, United States
  • Weinstein, Alan Mark, Weill Medical College of Cornell, New York, New York, United States
  • Palmer, Lawrence G., Weill Medical College of Cornell, New York, New York, United States
  • Wang, Tong, Yale University, New Haven, Connecticut, United States
Background

The thiazide-sensitive Na-Cl cotransporter (NCC) plays a key role in controlling NaCl absorption in the distal tubule, and also modulates salt and fluid delivery to downstream portions of the nephron, thus regulating K secretion. Previously we reported that higher NCC expression correlates with activity in female WT, and that gender-specific differences were absent in AT1a receptor knockout (KO) mice. We have now studied the gender difference in response to high K intake in WT and AT1a receptor KO animals.

Methods

Renal clearance experiments were performed on male WT and KO mice treated with normal and high K (5% KCl, 7 days) diets. Urine volume (UV), glomerular filtration rate (GFR), absolute (ENa, EK) and fractional (FENa, FEK) Na and K excretion were measured and compared at peak changes after a bolus iv injection of hydrochlorothiazide (HCTZ; 30mg/kg). Total NCC (tNCC) and Na/H-exchanger isoform 3 (NHE3) expressions in the kidney were examined by Western blotting.

Results

In WT mice, HK reduced tNCC abundance by 70% in females and by 60% in males. In KO mice HK produced more reduction of tNCC in male (60%) than female (33%). Functional measurements showed that in WT, K loading diminished HCTZ-dependent FENa by 53% in females and 42% in males. FENa was not reduced by high-K diet in KO mice. High-K intake significantly increased HCTZ-induced kaliuresis (EK) by 129% in WT male, but reduced EK in WT female (68%), KO male (51%) and KO female (55%). NHE3 expression was significantly reduced with high-K diet in all groups. There was no hyperkalemia in any group.

Conclusion

These results suggest that i) NCC activity decreases in response to a high-K diet, in part through decreased protein expression; ii) these responses depend on gender as well as on the presence of the AT1a receptor; iii) Proximal tubule function is also regulated by chronic high-K intake.

Funding

  • NIDDK Support