Effects of a high-sodium diet on renal tubule Ca2+transporter and claudin expression in Wistar-Kyoto rats

Abstract

BackgroundUrinary Ca2+ excretion increases with dietary NaCl. NaCl-induced calciuria may be associated with hypertension, urinary stone formation and osteoporosis, but its mechanism and long-term effects are not fully understood. This study examined alterations in the expressions of renal Ca2+ transporters, channels and claudins upon salt loading to better understand the mechanism of salt-induced urinary Ca2+ loss.MethodsEight-week old Wistar-Kyoto rats were fed either 0.3% or 8% NaCl diet for 8 weeks. Renal cortical expressions of Na+/Ca2+ exchanger 1 (NCX1), Ca2+ pump (PCMA1b), Ca2+ channel (TRPV5), calbindin-D28k, and claudins (CLDN-2, -7, -8, -16 and −19) were analyzed by quantitative PCR, western blot and/or immunohistochemistry.ResultsFractional excretion of Ca2+ increased 6.0 fold with high-salt diet. Renal cortical claudin-2 protein decreased by approximately 20% with decreased immunological staining on tissue sections. Claudin-16 and −19 expressions were not altered. Renal cortical TRPV5, calbindin-D28k and NCX1 expressions increased 1.6, 1.5 and 1.2 fold, respectively.ConclusionsChronic high-salt diet decreased claudin-2 protein and increased renal TRPV5, calbindin-D28k, and NCX1. Salt loading is known to reduce the proximal tubular reabsorption of both Na+ and Ca2+. The reduction in claudin-2 protein expression may be partly responsible for the reduced Ca2+ reabsorption in this segment. The concerted upregulation of more distal Ca2+-transporting molecules may be a physiological response to curtail the loss of Ca2+, although the magnitude of compensation does not seem adequate to bring the urinary Ca2+ excretion down to that of the normal-diet group.

Protective Effect of Zinc; Against Salt Induced Macroscopic Changes in Humerus and Femur of Rats

“…This observation is also supported by Gibbs who reported that supercedance of hunger center by the thirst center during salt loading 42 can lead to increase in water intake with resultant net weight loss. 43 Same effects were seen by Yatabe 34 who demonstrated decrease in weight gain with significant result p˂0.05 after feeding high salt diet (0.8% NaCl) to a group of rats for eight weeks. This could be due to increased calcium excretion with subsequent volume expansion and competition between Na and Ca ions in proximal convoluted tubules.…”

“…21,34,35 Although, increase in the total body weight (RTBW) of all the groups during eight weeks was observed, rats in group C had highest weight gain of 54g followed by weight gain of 37g in experimental group B. Increase in weight was observed in both experimental groups but the least weight gain of 22g was observed in group A fed on high salt diet.…”

“…19,20 due to change in bone mineral density and detrimental effect on calcium homeostasis. 21,22 Zinc is a component of more than 200 enzymes 14,23 and 23 most abundant element in the earth's crust with enzymatic function reduces osteoclast resorption activities and increase markers of osteoblast differentiation, matrix maturation and mineralization. 24 Zinc may increase bone formation through stimulating cell proliferation, alkaline phosphatase activity and collagen synthesis.…”

The role of calbindin-D28k on renal calcium and magnesium handling during treatment with loop and thiazide diuretics

“…Rizzo et al (20) found that bumetanide, a loop diuretic, upregulates CBD28k. Yatabe et al (25) reported that a high-sodium diet upregulates TRPV5, CBD-28k, and the Na/Ca exchanger (25). It has been suggested that the concerted upregulation of more distal Ca 2ϩ -and Mg 2ϩ -transporting molecules may be a physiological response to reduce the loss of Ca and Mg.…”

Effects of renal Na+/Ca2+ exchanger 1 inhibitor (SEA0400) treatment on electrolytes, renal function and hemodynamics in rats

“…Urine was collected for 24 h using metabolic cages. Sodium, potassium, creatinine, plasma renin activity, plasma aldosterone concentration, and urinary protein concentrations were determined as described previously [14,15,16]. FGF23 concentration in serum or plasma was determined using FGF-23 ELISA kit (KAINOS Laboratories, Tokyo, Japan), and serum 1,25 (OH) 2 vitamin D concentration was determined by SRL, Inc. (Tokyo, Japan) using radioimmunoassay.…”