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 (Ca2+) and magnesium (Mg2+) levels, we hypothesized that dietary Na+ and K+ intake affects Ca2+ and Mg2+ transport in the DCT. Therefore, the present study aimed to investigate the effect of a high Na+/low K+ diet on renal Ca2+ and Mg2+ handling. Mice were divided in 4 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. While Mg2+ homeostasis was not affected, the mice had elevated urinary Ca2+ and phosphate (Pi) excretion upon high Na+ intake, as well as significantly lower serum Ca2+ levels in the high Na+/low K+ group. Alterations in the gene and protein expression of players involved in Ca2+ 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.
American journal of physiology. Renal physiology. 2018 Jan 10 [Epub ahead of print]
Jenny van der Wijst, Omar A Z Tutakhel, Caro Bos, A H Jan Danser, Ewout J Hoorn, Joost G J Hoenderop, René J M Bindels
Physiology, Radboud university medical center, Netherlands., 286 Physiology, Radboud university medical center., Physiology, Radboud university medical center., Internal Medicine, Div. of Pharmacology and Vascular Medicine, Erasmus MC, Netherlands., Internal Medicine, Nephrology & Transplantation, Erasmus University, Netherlands., Physiology, Radboud university medical centre, Netherlands., Department of Physiology, Radboud university medical center, Netherlands.