Dissociation of sodium-chloride cotransporter expression and blood pressure during chronic high dietary potassium supplementation

TY - JOUR

T1 - Dissociation of sodium-chloride cotransporter expression and blood pressure during chronic high dietary potassium supplementation

AU - Little, Robert

AU - Murali, Sathish K.

AU - Poulsen, Søren B.

AU - Grimm, Paul R.

AU - Assmus, Adrienne

AU - Cheng, Lei

AU - Ivy, Jessica R.

AU - Hoorn, Ewout J.

AU - Matchkov, Vladimir

AU - Welling, Paul A.

AU - Fenton, Robert A.

PY - 2023/3

Y1 - 2023/3

N2 - Dietary potassium (K+) supplementation is associated with a lowering effect in blood pressure (BP), but not all studies agree. Here, we examined the effects of short- and long-term K+ supplementation on BP in mice, whether differences depend on the accompanying anion or the sodium (Na+) intake and molecular alterations in the kidney that may underlie BP changes. Relative to the control diet, BP was higher in mice fed a high NaCl (1.57% Na+) diet for 7 weeks or fed a K+free diet for 2 weeks. BP was highest on a K+-free/high NaCl diet. Commensurate with increased abundance and phosphorylation of the thiazide sensitive sodium-chloride-cotransporter (NCC) on the K+-free/high NaCl diet, BP returned to normal with thiazides. Three weeks of a high K+ diet (5% K+) increased BP (predominantly during the night) independently of dietary Na+ or anion intake. Conversely, 4 days of KCl feeding reduced BP. Both feeding periods resulted in lower NCC levels but in increased levels of cleaved (active) α and γ subunits of the epithelial Na+ channel ENaC. The elevated BP after chronic K+ feeding was reduced by amiloride but not thiazide. Our results suggest that dietary K+ has an optimal threshold where it may be most effective for cardiovascular health.

AB - Dietary potassium (K+) supplementation is associated with a lowering effect in blood pressure (BP), but not all studies agree. Here, we examined the effects of short- and long-term K+ supplementation on BP in mice, whether differences depend on the accompanying anion or the sodium (Na+) intake and molecular alterations in the kidney that may underlie BP changes. Relative to the control diet, BP was higher in mice fed a high NaCl (1.57% Na+) diet for 7 weeks or fed a K+free diet for 2 weeks. BP was highest on a K+-free/high NaCl diet. Commensurate with increased abundance and phosphorylation of the thiazide sensitive sodium-chloride-cotransporter (NCC) on the K+-free/high NaCl diet, BP returned to normal with thiazides. Three weeks of a high K+ diet (5% K+) increased BP (predominantly during the night) independently of dietary Na+ or anion intake. Conversely, 4 days of KCl feeding reduced BP. Both feeding periods resulted in lower NCC levels but in increased levels of cleaved (active) α and γ subunits of the epithelial Na+ channel ENaC. The elevated BP after chronic K+ feeding was reduced by amiloride but not thiazide. Our results suggest that dietary K+ has an optimal threshold where it may be most effective for cardiovascular health.

UR - http://www.scopus.com/inward/record.url?scp=85150000749&partnerID=8YFLogxK

U2 - 10.1172/jci.insight.156437

DO - 10.1172/jci.insight.156437

M3 - Journal article

C2 - 36719746

AN - SCOPUS:85150000749

SN - 2379-3708

VL - 8

JO - JCI Insight

JF - JCI Insight

IS - 5

M1 - e156437

ER -