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 7

Short-term and chronic KCl feeding have opposing effects on BP.

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Short-term and chronic KCl feeding have opposing effects on BP. (A and B...
(A and B) Short-term (4 days) high KCl feeding combined with a normal NaCl diet (NS/+KCl) significantly reduces SBP recorded from implanted telemetry probes across 24 hours (n = 4/diet) (A) and over 24 hours as defined by MESOR or during the 12 hours dark or light phase (B), compared with control diet (NS/NK). The magnitude of error from the mean may be less than the smallest size of symbol available.(C and D) SBP and DBP recorded using tail cuff plethysmography during the dark phase are significantly lower during short-term (4 days) high KCl feeding but significantly higher during chronic KCl feeding (3 weeks) compared with control-fed animals (NS/NK). Chronic 0K feeding (2 weeks) significantly increases SBP and DBP compared with NS/NK-fed animals. (E) A single of dose of hydrochlorothiazide (HCTZ) 4 hours before tail cuff recording significantly reduced SBP of NS/NK-fed animals, but not short-term NS/+KCl-fed animals; it had no significant effect on elevated SBP in chronically fed NS/+KCl animals. Data were analyzed by 2-tailed t test between 2 groups (B), using a 1-way ANOVA followed by Dunnett’s multiple-comparison test (3 groups, C and D), or by 2-way ANOVA followed by Tukey’s multiple-comparison testing (E). *P < 0.05; **P < 0.01; ****P < 0.0001. All data are shown as mean ± SEM, with individual values shown.