Abstract: SA-PO0477
Humanized Diets Define Optimal Pressure-Lowering Response to Dietary Potassium in Mice
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Basic Research
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic
Authors
- Welling, Paul A., Johns Hopkins Medicine, Baltimore, Maryland, United States
- Grimm, Rick, Johns Hopkins Medicine, Baltimore, Maryland, United States
- Al-Qusairi, Lama, Johns Hopkins Medicine, Baltimore, Maryland, United States
- Ellison, David H., Oregon Health & Science University, Portland, Oregon, United States
- Fenton, Robert A., Aarhus Universitet, Aarhus, Central Denmark Region , Denmark
- Jung, Hyun Jun, Johns Hopkins Medicine, Baltimore, Maryland, United States
Background
High-potassium (K) diets lower blood pressure (BP) in rodents and humans but can also raise BP when consumed in excessive amounts. We reported (JCI Insight, 2023) the K-mediated BP lowering response, driven by the inactivation of the thiazide-sensitive sodium chloride cotransporter (NCC), is offset by an increase in Epithelial Sodium Channel (ENaC) and tubule injury responses when an extremely high K diet is chronically consumed. Here, we define the optimal dietary K level that inactivates NCC without activating ENaC and injury responses.
Methods
Male mice (C57Bl6J) were fed high-sodium diets containing six different K contents, comparing the control diet (1% K) with traditional extremes (0.1% and 5% K) and those that mimic a range of K levels found in human diets (0.35%, 0.7%, and 1.7%). NCC- (hydrochlorothiazide-sensitive) and ENaC- (benzamil-sensitive) dependent sodium handling was assessed in clearance studies. BP was measured by telemetry. Single-nucleus RNA sequencing (snRNA-Seq) characterized the transcriptomic responses to the K diets. NCC and ENaC Protein abundance and post-translational activation were evaluated by Western Blot and immunofluorescence microscopy.
Results
Systolic blood pressure during the active period exhibits a ‘U-shaped’ relationship with dietary K, with the lowest blood pressure at 1.7% K. As potassium is reduced from 1.7% (0.1%, 0.35%, and 0.7% K groups), BP, NCC phosphorylation, and thiazide sensitivity increase; however, they become benzamil-sensitive in the 5% K group, as ENaC cleavage increases. Aldosterone levels increase with increasing dietary K, but are significantly lower in the 0.1%, 0.35%, and 0.7% groups compared to the control group. snRNA-seq revealed that the transcriptomes of the proximal tubule and CNT were most significantly altered by K+ diets, with distinct changes for each K diet and cell type, illuminating new pathways enriched in ion transport and morphogenetic processes that may contribute to the effects of K on BP.
Conclusion
An optimal dietary K level (1.7%) that maximally reduces BP in mice by suppressing NCC activity, limiting aldosterone activation of ENaC, and regulating transport and tubule remodeling pathways in the proximal tubule and CNT was defined. This diet mimics the human DASH diet in K content and further supports its efficacy as a BP-lowering tool.
Funding
- NIDDK Support