Renal Acidification Defect Induced by Lithium in Control and Acidotic Rats

Abstract

1. The aim of this work was to contribute to a better understanding of the mechanism by which Li+ administration impairs renal tubular acidification. 2. The kinetics of tubular acidification in the mid-proximal and distal convoluted tubules were studied by measuring intratubular pH using Sb microelectrodes during stopped-flow microperfusion with Krebs-Ringer bicarbonate (30 mmol/l) buffer. Four groups of male Wistar rats were utilized in this study: control, control plus lithium (C + Li+; one intraperitoneal injection of LiCl of 4 mmol l−1 day−1 kg−1 for 4 days), acidotic and acidotic plus lithium (A+ Li+). 3. In C + Li+ rats, the half-time of acidification was significantly higher than in control rats (P < 0.01), in both the mid-proximal tubule (11.3 ± 0.34 vs 6.73 ± 0.22 s) and the distal convoluted tubule (17.5 ± 0.31 vs 11.5 ± 1.02 s), and net HCO3− reabsorption was lower in both the mid-proximal tubule and the distal convoluted tubule. The effects of Li+ on tubular acidification kinetics were similar in acidotic rats. 4. A net Na+ flux, as measured by the Gertz split-droplet method, was significantly decreased in the mid-proximal tubule (P < 0.01) in C + Li+ rats compared with control rats (2.14 ± 0.17 vs 4.07 ± 0.39 nmol s−1 cm−2). 5. The transepithelial potential difference in the distal convoluted tubule was significantly lower (P < 0.01) in C + Li+ rats than in control rats (–7.50 ± 1.50 vs −20.5 ± 1.12 mV). 6. These findings suggest that Li+ causes a reduction in the apical Na+ gradients in both tubular segments, thereby decreasing the favourable driving force for H+ secretion.