Effects of extreme potassium stress on blood pressure and renal tubular sodium transport

• Published in: American journal of physiology. Renal physiology 2020-06, Vol.318 (6), p.F1341-F1356
• Main Authors: Boyd-Shiwarski, Cary R, Weaver, Claire J, Beacham, Rebecca T, Shiwarski, Daniel J, Connolly, Kelly A, Nkashama, Lubika J, Mutchler, Stephanie M, Griffiths, Shawn E, Knoell, Sophia A, Sebastiani, Romano S, Ray, Evan C, Marciszyn, Allison L, Subramanya, Arohan R
• Format: Article
• Language: English
• Subjects: Amiloride; Animal Feed; Animals; Arterial Pressure; Blood pressure; Diabetes; Diabetes insipidus; Diabetes Insipidus - etiology; Diabetes Insipidus - metabolism; Diabetes Insipidus - physiopathology; Diet; Epidemiology; Epithelial Sodium Channels - metabolism; Furosemide; Hypertension - etiology; Hypertension - metabolism; Hypertension - physiopathology; Ion Transport; Kidney Tubules - metabolism; Kidney Tubules - physiopathology; Male; Mice, 129 Strain; Natriuresis; Nutrient deficiency; Phosphorylation; Potassium chloride; Potassium Deficiency - etiology; Potassium Deficiency - metabolism; Potassium Deficiency - physiopathology; Potassium, Dietary - administration & dosage; Potassium, Dietary - metabolism; Potassium, Dietary - toxicity; Sodium; Sodium chloride; Sodium Chloride Symporters - metabolism; Sodium Chloride, Dietary - metabolism; Sodium Chloride, Dietary - toxicity; Sodium-Potassium-Chloride Symporters - metabolism; Sulfate Transporters - metabolism
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00527.2019

We characterized mouse blood pressure and ion transport in the setting of commonly used rodent diets that drive K intake to the extremes of deficiency and excess. Male 129S2/Sv mice were fed either K -deficient, control, high-K basic, or high-KCl diets for 10 days. Mice maintained on a K -deficient diet exhibited no change in blood pressure, whereas K -loaded mice developed an ~10-mmHg blood pressure increase. Following challenge with NaCl, K -deficient mice developed a salt-sensitive 8 mmHg increase in blood pressure, whereas blood pressure was unchanged in mice fed high-K diets. Notably, 10 days of K depletion induced diabetes insipidus and upregulation of phosphorylated NaCl cotransporter, proximal Na transporters, and pendrin, likely contributing to the K -deficient NaCl sensitivity. While the anionic content with high-K diets had distinct effects on transporter expression along the nephron, both K basic and KCl diets had a similar increase in blood pressure. The blood pressure elevation on high-K diets correlated with increased Na -K -2Cl cotransporter and γ-epithelial Na channel expression and increased urinary response to furosemide and amiloride. We conclude that the dietary K maneuvers used here did not recapitulate the inverse effects of K on blood pressure observed in human epidemiological studies. This may be due to the extreme degree of K stress, the low-Na -to-K ratio, the duration of treatment, and the development of other coinciding events, such as diabetes insipidus. These factors must be taken into consideration when studying the physiological effects of dietary K loading and depletion.