THE EFFECT OF CHRONIC SODIUM DEPLETION ON RENAL-FUNCTION IN CONSCIOUSRATS

In order to investigate the effect of chronic sodium depletion on rena l proximal tubular reabsorption, studies were performed in conscious, unrestrained Brattleboro rats. Since these animals lack circulating va sopressin, fractional water reabsorption in the distal nephron can be assumed to be constant and changes in urine flow rate should therefore reflect changes in end-proximal fluid delivery. Sodium depletion was induced by placing rats on a low-sodium diet (4 mmol Na (kg dry wt)-1) and administering frusemide (40 mg (kg body wt)-1) by gavage on the f irst 2 days. Extracellular volume, measured after 7-9 days, was reduce d by 19 % (P < 0.02) as compared with that of rats maintained on a con trol diet. Urine flow rate, measured during days 4-7 of the low-sodium diet, was significantly lower than that of control rats (142 +/- 8 vs . 168 +/- 5 ml day-1, P < 0.0 1). Since renal papillary interstitial f luid osmolality was found to be reduced in the sodium-depleted rats (6 93 +/- 38 vs. 812 +/- 36 mosmol (kg H2O)-1, P < 0.05), it is unlikely that water reabsorption from sites beyond the proximal tubule had incr eased. The observed reduction in urine flow rate therefore strongly su ggests a reduction in end-proximal fluid delivery. In the second part of the study, a single group of Brattleboro rats was used, in which os motic minipumps were implanted in the peritoneal cavity for continuous infusion of [C-14]inulin. After recovery from the operation, the rats were maintained on a control diet for 6 days (pre-control period), th en subjected to sodium depletion (low-sodium diet for 6 days, frusemid e administration on the first 2 days), and finally returned to the con trol diet for 6 days, with access to 0.46 m NaCl solution on the first 2 days, in order to restore sodium balance (post-control period). On the final 2 days of each phase, urine flow rate and [C-14]inulin clear ance (= glomerular filtration rate, GFR) were measured. Urine flow rat es during the pre-control, sodium depletion and post-control periods w ere 169+7, 132 +/- 8 (P < 0.001) and 176 +/- 8 mul min-1, respectively ; corresponding values for fractional water excretion were 7.0 +/- 0.3 , 6.0 +/- 0.5 (P < 0.01) and 7.4 +/- 0.4%. Only a small reduction in G FR, of borderline statistical significance, was observed during sodium depletion. We conclude that chronic sodium depletion causes a reducti on in end-proximal fluid delivery which is largely a consequence of en hanced fractional fluid reabsorption in the proximal tubule.