Dietary K⁺ acts as a genuine diuretic

Abstract

K + balance in mammals relies on regulated renal K + excretion matching unregulated fluctuating K + intake. Upon a K + rich meal, rapid and powerful K + excretion is needed. Renal K + secretion is stimulated by the increased tubular flow.We speculated that high K + intake acutely increases urinary flow to stimulate K + excretion.Methods: Mice were K + challenged through diets or gavage. Post K + loading urinary output, osmolarity, [K + ] u , [Na + ] u , plasma osmolarity, [copeptin] p , [K + ] p , and [Na + ] p were measured. To locate the mechanism of K + -induced diuresis in the glomerular/tubular system we measured creatinine excretion and assessed functional transport in isolated perfused TALs and CDs during an acute [K + ] bl switch from 3.6 to 6.5 mM. Molecular adaptations of transport proteins involved in water reabsorption were investigated by immunoblotting. Results:(1) Mice switched from a 1% to 2% K + diet increased diuresis within 12 hours and reciprocally reduced diuresis when switched from 1% to 0.01% K + diet. (2) A single K + gavage load, corresponding to 25%-50% of daily K + intake, induced 100% increase in diuresis within 30 minutes. This occurred despite augmented plasma osmolarity and AVP synthesis. (3) K + gavage did not change GFR.(4) In isolated perfused TALs, shifting [K + ] bl from 3.6 to 6.5 mM did not affect AVP-induced NaCl transport. (5) In sharp contrast, in isolated perfused CDs, shifting [K + ] bl from 3.6 to 6.5 mM markedly reduced CD AVP sensitivity, ie inhibited water absorption. Conclusion:Dietary K + loading induces a rapidly on-setting diuresis. The mechanism of K + -induced diuresis involves desensitization of the CD to AVP. K E Y W O R D Santi-diuretic hormone, direct K + effect, diuresis, K + homeostasis, urinary K + excretion | INTRODUCTIONIn 1928, the Canadian physician William L. T. Addison showed that K + rich diets reduce blood pressure, whereas Na + rich diets had the opposite effect. 1 Numerous randomized trials have since then shown that a diet enriched with K + is associated with protection against hypertension, cardiovascular disease, and overall mortality. 2 These effects are not completely understood but are most likely associated with functional and molecular adaptations in renal water and salt handling. 3

Loss of the Secretin Receptor Impairs Renal Bicarbonate Excretion and Aggravates Metabolic Alkalosis in Mice during Acute Base-Loading

“…Tissue harvesting for Western blots was performed as described previously. 34,35 In short, blotting was performed on the supernatant of half kidneys processed in lysis buffer with a tissuelyser (Qiagen) for 30 seconds and spun for 15 minutes (1000 g).…”

“…Kidneys from SCTR WT and KO mice were fixed by perfusion by 4% paraformaldehyde in PBS, embedded in paraffin, sectioned, and immunolabelled for pendrin (primary antibody 32 ) diluted 1:1200, secondary antibody (P0048 DAKO, Glostrup, Denmark, coupled with horse radish peroxidase) following protocol A in Paulsen et al 33 Immunoblotting Tissue harvesting for Western blots was performed as described previously. 34,35 In short, blotting was performed on the supernatant of half kidneys processed in lysis buffer with a tissuelyser (Qiagen) for 30 seconds and spun for 15 minutes (1000 g).…”

Potassium Homeostasis and WNK Kinases in the Regulation of the Sodium-Chloride Cotransporter: Hyperaldosteronism and Its Metabolic Consequences

“…Part of the benefit of K 1 -rich diets is attributed to their natriuretic effect (20,21). Reduced dietary K 1 content promotes Na 1 retention, whereas K 1 supplementation has the opposite effect.…”