Abstract
The distal convoluted tubule (DCT) of the kidney plays an important role in blood pressure regulation by modulating Na(+) reabsorption via the Na(+)-Cl(-) cotransporter (NCC). A diet containing high salt (NaCl) and low K(+) activates NCC, thereby causing Na(+) retention and a rise in blood pressure. Since high blood pressure, hypertension, is associated with changes in serum calcium (Ca(2+)) and magnesium (Mg(2+)) levels, we hypothesized that dietary Na(+) and K(+) intake affects Ca(2+) and Mg(2+) transport in the DCT. Therefore, the present study aimed to investigate the effect of a high-Na(+)/low-K(+) diet on renal Ca(2+) and Mg(2+) handling. Mice were divided in four groups and fed a normal-Na(+)/normal-K(+), normal-Na(+)/low-K(+), high-Na(+)/normal-K(+), or high-Na(+)/low-K(+) diet for 4 days. Serum and urine were collected for electrolyte and hormone analysis. Gene and protein expression of electrolyte transporters were assessed in kidney and intestine by qPCR and immunoblotting. Whereas Mg(2+) homeostasis was not affected, the mice had elevated urinary Ca(2+) and phosphate (Pi) excretion upon high Na(+) intake, as well as significantly lower serum Ca(2+) levels in the high-Na(+)/low-K(+) group. Alterations in the gene and protein expression of players involved in Ca(2+) and Pi transport indicate that reabsorption in the proximal tubular and TAL is affected, while inducing a compensatory response in the DCT. These effects may contribute to the negative health impact of a high-salt diet, including kidney stone formation, chronic kidney disease, and loss of bone mineral density.
