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

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.