The effect of chronic sodium depletion on renal function in conscious rats

Abstract

SUMMARYIn order to investigate the effect of chronic sodium depletion on renal proximal tubular reabsorption, studies were performed in conscious, unrestrained Brattleboro rats. Since these animals lack circulating vasopressin, fractional water reabsorption in the distal nephron can be assumed to be constant and changes in urine flow rate should therefore reflect changes in endproximal 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 first 2 days. Extracellular volume, measured after 7-9 days, was reduced by 19 % (P < 0 02) as compared with that of rats maintained on a control 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-', P < 0 01). Since renal papillary interstitial fluid osmolality was found to be reduced in the sodium-depleted rats (693 + 38 vs. 812 + 36 mosmol (kg H2O)-', P < 0 05), it is unlikely that water reabsorption from sites beyond the proximal tubule had increased. The observed reduction in urine flow rate therefore strongly suggests a reduction in end-proximal fluid delivery. In the second part of the study, a single group of Brattleboro rats was used, in which osmotic minipumps were implanted in the peritoneal cavity for continuous infusion of[14C]inulin. After recovery from the operation, the rats were maintained on a control diet for 6 days (pre-control period), then subjected to sodium depletion (low-sodium diet for 6 days, frusemide administration on the first 2 days), and finally returned to the control diet for 6 days, with access to 0 46 M NaCl solution on the first 2 days, in order to restore sodium balance (postcontrol period). On the final 2 days of each phase, urine flow rate and [14C]inulin clearance (= glomerular filtration rate, GFR) were measured. Urine flow rates during the pre-control, sodium depletion and post-control periods were 169+7, 132+8 (P<0-001) and 176+8 1l 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 GFR, of borderline statistical significance, was observed during sodium depletion. We conclude that chronic sodium depletion causes a reduction in end-proximal fluid delivery which is largely a consequence of enhanced fractional fluid reabsorption in the proximal tubule.

A micropuncture study of renal tubular lithium reabsorption in sodium‐depleted rats.

“…Sodium depletion was achieved by the administration of a large dose of frusemide followed by maintenance on a sodiumdeficient diet for 8-10 days. A similar protocol has been shown to cause a substantial reduction in extracellular fluid volume (Shirley & Skinner, 1994); this is also suggested in the present study by the raised haematocrit and plasma protein concentration. The glomerular filtration rate was found to be slightly reduced in sodiumdepleted animals.…”

“…However, it is notable that the reduction in CLi in the sodium-restricted rats of Shalmi & Thomsen was minor compared with that observed in the present and previous studies (Thomsen & Leyssac, 1986;Shirley et al 1989;Shalmni et al 1990). …”

“…Although recent micropuncture studies in rats infused with the loop diuretic frusemide have suggested that a small amount of lithium may additionally be reabsorbed in the loop of Henle (Shirley, Walter & Sampson, 1992;Fransen, Boer, Boer, Dorhout Mees & Koomans, 1993), on balance it seems that C%j may normally provide a reasonable index of end-proximal fluid delivery . However, when rats are fed a low sodium diet, values for CLi and fractional lithium excretion (FELl) fall to extremely low levels (Thomsen & Leyssac, 1986;Kirchner, 1987;Shirley, Skinner & Walter, 1989;Shalmi, Petersen, Thomsen & Christensen, 1990) and it is widely believed that in this situation a significant amount of filtered lithium is reabsorbed beyond the loop of Henle. This view is supported by the observation that amiloride, a diuretic whose principal site of action is the collecting tubule (Horisberger & Giebisch, 1987) and which in sodium-replete animals does not affect lithium reabsorption (Shirley et al 1992), increases Ciin sodium-depleted rats (Thomsen & Leyssac, 1986;Kirchner, 1987 On the day of micropuncture, each rat was anaesthetized with Inactin (120 mg kg-'; Byk Gulden, Konstanz, Germany) and prepared surgically as described in previous reports from this laboratory (Wralter, Laycock & Shirley, 1979;Shirley, Zewde & Walter, 1990).…”

Computational simulation of vasopressin secretion using a rat model of the water and electrolyte homeostasis

“…The value of Na + clearance used in the model (table 1) was calculated from experimental data reported in four distinct studies [21-24] and calculations are presented in Additional file 2. Na + clearance combined with the action of the AVP controller are however, not sufficient to overcome the small variations in ECF volume resulting from the change in ECF osmolality (data not shown).…”

Interactions Between Furosemide and the Renal Sympathetic Nerves

“…infusion. However, Shirley & Skinner (1994) demonstrated that chronic Na depletion decreased urine flow by 22% in conscious, unrestrained Brattleboro rats who lack circulating vasopressin. This was ascribed to increased fractional proximal tubular Na reabsorption and a small decrease in GFR.…”