Renal acidification defect induced by lithium in control and acidotic rats

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 less than 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 less than 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 less than 0.01) in C + Li+ rats than in control rats (-7.50 +/- 1.50 vs -20.5 +/- 1.12 mV).(ABSTRACT TRUNCATED AT 250 WORDS)