Dietary K⁺ acts as a genuine diuretic

TY - JOUR

T1 - Dietary K+ acts as a genuine diuretic

AU - Svendsen, Samuel L

AU - Kornvig, Simon

AU - Berg, Peder

AU - Jensen, Iben S

AU - de Araujo, Isabela B B A

AU - Larsen, Casper K

AU - Leipziger, Jens

AU - Sorensen, Mads V

PY - 2022/2

Y1 - 2022/2

N2 - 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 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 12h 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, i.e. 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.

AB - 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 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 12h 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, i.e. 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.

KW - Animals

KW - Diet

KW - Diuresis

KW - Diuretics/pharmacology

KW - Kidney/metabolism

KW - Mammals

KW - Mice

KW - Sodium/metabolism

UR - http://www.scopus.com/inward/record.url?scp=85122751832&partnerID=8YFLogxK

U2 - 10.1111/apha.13762

DO - 10.1111/apha.13762

M3 - Journal article

C2 - 34984847

SN - 1748-1708

VL - 234

JO - Acta Physiologica

JF - Acta Physiologica

IS - 2

M1 - e13762

ER -