Abstract: TH-PO321
Maintaining Potassium Balance on the High-Potassium Alkaline Diet via Proximal Tubule RAS-Stimulated Sodium Delivery
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Basic
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid‚ Electrolyte‚ and Acid-Base Disorders
- 1001 Fluid‚ Electrolyte‚ and Acid-Base Disorders: Basic
Authors
- Wang, Bangchen, Duke University Health System, Durham, North Carolina, United States
- Wang-France, Jun, University of Nebraska Medical Center, Omaha, Nebraska, United States
- Sansom, Steven C., University of Nebraska Medical Center, Omaha, Nebraska, United States
Background
The angiotensin II (ANGII) activated WNK4-SPAK pathway regulates the Na, Cl cotransporter (NCC) in the distal convoluted tubule (DCT) to control the Na delivered to the connecting tubule (CNT) and cortical collecting duct (CCD), where it stimulates K secretion as a mechanism to maintain K balance (3.6 mM < P[K] < 5.5 mM). We previously found that K balance was maintained in mice given a 5% K diet that was accompanied by alkaline loading anions (HK) but not by acid-loading anions (HK-Cl). We designed these experiments to determine whether HK enhances Na delivery as a mechanism to stimulate K secretion and whether ROMK and ANGII were involved in this process.
Methods
Wild type (WT), ROMK knockout (ROMK-KO), liver angiotensinogen II knockout (LKO), and liver plus proximal tubule angiotensinogen double knockout mice (DKO) were given either a high K diet with alkaline loading anions (HK; 5% K-citrate/carbonate/Cl) or a high K diet with acid loading anions (HK-Cl; 5% KCl) and placed in metabolic cages for 6 days. Glomerular filtration rate (GFR) was determined by FITC-inulin. Urine and plasma [Na] and [K] were determined by flame photometry. Urine pH was determined by a Mettler Toledo pH meter. The AT2 agonist, compound 21 (C21) was given to a group of DKO mice at 5 mg/Kg/min for 6 days.
Results
When WT were given HK (n=13) and HK-Cl (n=15), the respective means ±SEM of urine pH were 8.40 ±0.52 and 5.68 ±0.49, P[K] were 4.62 mM ±0.16 and 5.72 ±0.30 mM, and rates of Na excretion (UNaV; mmole/day) were 428.8 ±29.6 and 289.3 ±22.7. GFR was not significantly different between HK (370.8 ±20.2 ml/day; n=6) and HK-Cl (419.9 ±19.7 ml/day; n=5). When ROMK-KO was given HK (n=9) and HK-Cl (n=7), the P[K] was 5.15 ±0.17 mM and 6.37 ±0.35 mM, respectively and the UNaV was 308.2 ±20.2 and 194.2 ±12.0, respectively. When given HK, LKO (P[K] = 4.52 ±0.11 mM, n=4), but not DKO (P[K] = 7.0 ±1.0 mM, n=4), maintained K balance. C21 restored K balance in DKO on HK (P[K] = 4.28 ±0.25 mM, n=3) and increased UNaV from 177.8 ±25.3 to 326.9 ±58.6 (n=3).
Conclusion
These results show that: 1. The thick ascending limb and ROMK were not involved in the ability of HK mice to enhance Na delivery and maintain K balance. 2. For HK mice, PT-generated ANGII, via AT2 receptors, enhances Na delivery to the CNT and CCD to stimulate K secretion and maintain K balance.
Funding
- NIDDK Support