Dissociation of sodium-chloride cotransporter expression and blood pressure during chronic high dietary potassium supplementation
Robert Little, Sathish K. Murali, Søren B. Poulsen, Paul R. Grimm, Adrienne Assmus, Lei Cheng, Jessica R. Ivy, Ewout J. Hoorn, Vladimir Matchkov, Paul A. Welling, Robert A. Fenton
Robert Little, Sathish K. Murali, Søren B. Poulsen, Paul R. Grimm, Adrienne Assmus, Lei Cheng, Jessica R. Ivy, Ewout J. Hoorn, Vladimir Matchkov, Paul A. Welling, Robert A. Fenton
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Research Article Nephrology

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

Abstract

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.

Authors

Robert Little, Sathish K. Murali, Søren B. Poulsen, Paul R. Grimm, Adrienne Assmus, Lei Cheng, Jessica R. Ivy, Ewout J. Hoorn, Vladimir Matchkov, Paul A. Welling, Robert A. Fenton

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Figure 8

Potassium and aldosterone are elevated in high-KCl–fed animals.

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Potassium and aldosterone are elevated in high-KCl–fed animals. (A) Plas...
(A) Plasma [aldosterone] is increased following short-term and chronic KCl feeding. Chronic 0K feeding (2 weeks) significantly reduced [aldosterone]. HS diet reduced [aldosterone] across all groups. Only 2 HS/0K-fed animals had a detectable level of aldosterone, so this condition was not analyzed. Data were analyzed as 2-way ANOVA with Dunnett’s multiple-comparison testing. (B) Urine aldosterone concentrations under the different chronic dietary K+ conditions. Data were analyzed by a 2-way ANOVA main effects model, with multiple comparisons with NS/NK group. (C) Urine aldosterone excretion was significantly higher during the 12-hour dark phase (18:00–06:00) compared with the light phase, with the magnitude of increase clearly being greater for high-KCl–fed (+KCl-fed) animals. No clear difference was detected between short-term (4 days) and chronically (3 week) fed animals. Analysis within groups by 2-tailed t test. (D) Plasma [K+] under the different short-term or chronic dietary K+ conditions. Data are shown as mean ± SEM, with individual values shown. Data were analyzed as 2-way ANOVA with Dunnett’s multiple-comparison testing. (E) Urine aldosterone concentration significantly positively correlates with plasma K+ concentration. Best fit analysis, linear regression, with 95% CI limits (dotted lines) displayed. Data are shown as mean ± SEM. (F) The relationship between SBP against plasma [K+] fits a second order quadratic equation. Data are from individuals where BP and blood sampling are made from same animal. All individual values considered for best-fit nonlinear regression.*P < 0.05; **P < 0.01; ***P < 0.001. ##P < 0.01, ###P < 0.001 versus respective chronic NS condition.