Micropuncture study of hypertonic mannitol diuresis in the proximal and distal tubule of the dog kidney

Abstract

A B S T R A C T Fractional reabsorption of water, sodium, and potassium at proximal and distal tubular sites within the nephron was studied by recollection-micropuncture experiments on dogs undergoing hypertonic mannitol diuresis. After an initial control hydropenic phase, 16% mannitol in modified Ringer's solution was administered intravenously, resulting in marked increases in fractional excretion of water (28.7%), sodium (12.6%), and potassium (63.9%). Inulin clearance decreased significantly from 35.1 to 25.2 ml/min. Analysis of paired micropuncture data revealed a significant decrease in tubule fluid to plasma (TF: P) inulin ratios in both the proximal tubule (1.63-1.45) and distal tubule (5.38-1.94). There was also a significant decrease in proximal TF: P sodium ratios (0.99-0.93) and potassium ratios (1.05-0.98). Distal TF: P sodium ratios, in contrast, rose significantly (0.38-0.59), while TF: P potassium ratios tended towards unity whether initially greater or less than one. Fractional reabsorption of sodium and water decreased by 5% and 10% respectively in the proximal tubule, but to a lesser extent than the resulting increases in fractional urinary excretion. The nonreabsorbed fraction, however, had increased sharply at the point of distal puncture for water (32%), sodium (26%), and potassium (26%), indicating a large inhibitory effect within the loop of Henle in addition to the smaller proximal effects.

Effects of Acute Volume Expansion and Altered Hemodynamics on Renal Tubular Function in Chronic Caval Dogs

“…The ratio of the second TF/P inulin to the first was 1.04 ±0.02 (SEM). These results are comparable with those reported by other investigators working in the dog (18). Table IV summarizes the data obtained from distal tubule micropuncture.…”

“…These investigators demonstrated that the infusion of mannitol into edematous patients was more efficacious in augmenting free water clearance than in normal controls, and interpreted their findings to mean that there was hyperreabsorption of filtrate in the proximal tubules of the patients with edema. However, in a recent micropuncture study, Seely and Dirks (18) have demonstrated that at least in the dog, mannitol has only a minimal effect in the proximal tubule and exercises its major osmotic effect in the loop of Henle. As these authors point out, an inhibitory effect of mannitol in the descending limb of the loop is not necessarily incompatible with clearance studies which have demonstrated that mannitol infusions increase free water clearance.…”

Effects of chronic, urea-induced osmotic diuresis on kidney weight and function in rats

“…Brown et al [13] suggested that the effects of osmotic diuresis observed in diabetic nephropathy should be studied in isolation from hypergly-caemia, using a simple model that excludes other variables. For example, mannitol injections have been used to experimentally induce osmotic diuresis in normal rats [14]. However, osmotic diuresis associated with hyperglycaemia has been shown to be markedly different from osmotic diuresis induced by mannitol or a hypertonic sodium chloride solution [15][16][17].…”

Diuretics: a review

“…It therefore increases the tubular fluid osmolality, which decreases water reabsorption. 36 All osmotic diuretics, including mannitol, exert their effect at nephron sites which have AQP water channels. Mannitol acts at the proximal tubule and thin descending limb of the loop of Henlé, both sites of AQP1 channels.…”

“…36 The lower gradient in osmolality between the tubular cells and lumen impairs water reabsorption, resulting in water diuresis and hypernatraemia. 37 Unlike any of the other diuretics, mannitol produces a water diuresis rather than a natriuresis; water being lost over and above sodium and potassium.…”