Effects of a high-sodium diet on renal tubule Ca(2+) transporter and claudin expression in Wistar-Kyoto rats

BACKGROUND: Urinary Ca(2+) 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 Ca(2+) transporters, channels and claudins upon salt loading to better understand the mechanism of salt-induced urinary Ca(2+) loss. METHODS: Eight-week old Wistar-Kyoto rats were fed either 0.3% or 8% NaCl diet for 8 weeks. Renal cortical expressions of Na(+)/Ca(2+) exchanger 1 (NCX1), Ca(2+) pump (PCMA1b), Ca(2+) channel (TRPV5), calbindin-D(28k,) and claudins (CLDN-2, -7, -8, -16 and −19) were analyzed by quantitative PCR, western blot and/or immunohistochemistry. RESULTS: Fractional excretion of Ca(2+) 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-D(28k) and NCX1 expressions increased 1.6, 1.5 and 1.2 fold, respectively. CONCLUSIONS: Chronic high-salt diet decreased claudin-2 protein and increased renal TRPV5, calbindin-D(28k), and NCX1. Salt loading is known to reduce the proximal tubular reabsorption of both Na(+) and Ca(2+). The reduction in claudin-2 protein expression may be partly responsible for the reduced Ca(2+) reabsorption in this segment. The concerted upregulation of more distal Ca(2+)-transporting molecules may be a physiological response to curtail the loss of Ca(2+), although the magnitude of compensation does not seem adequate to bring the urinary Ca(2+) excretion down to that of the normal-diet group.