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A B S T R A C T In previous reports from this laboratory we have suggested that a reduction in medullary tonicity decreases the thin ascending loop of Henle sodium reabsorption and is in part responsible for the magnitude for the natriuresis accompanying 10% body weight Ringer loading. According to this postulate, one would expect that the medullary washout associated with water diuresis would also result in a natriuresis, but this does not occur. It is possible, however, that increased delivery from the proximal tubule is necessary to demonstrate an effect of medullary tonicity on urinary sodium excretion. Micropuncture studies were designed to test that possibility by increasing distal delivery by 2% Ringer loading in animals with and without reduced medullary tonicity. In an initial series of experiments the a-adrenergic agonist clonidine was used to induce a water diuresis. When given alone, this agent caused a marked decrease in urine osmolality and an increase in urine flow rate but had no effect on proximal reabsorption in either superficial or juxtamedullary nephrons, and did not alter urinary sodium excretion. Volume expansion with 2% body weight Ringer solution resulted in a significant fall in proximal reabsorption and a trivial increment in sodium excretion. When this same degree of volume expansion was conferred on animals undergoing a water diuresis, a marked increase in absolute and fractional sodium excretion occurred. In a second group of studies medullary tonicity was reduced in the left kidney only by removal of the left ureter 1 h before micropuncture. When these animals were infused with 2% body weight Ringer solution, proximal reabsorption was decreased in juxtamedullary nephrons, and a marked increase in sodium excretion was observed only from the left kidney. Finally, the effect of water diuresis on fractional sodium delivery to the early and late distal tubule of superficial nephrons during 2% Ringer loading was evaluated. Delivery to both of these sites was comparable after 2% Ringer loading alone and during 2% Ringer loading plus water diuresis.From these data, we conclude that medullary tonicity does influence renal sodium handling but that this effect is manifest in the final urine only under conditions in which proximal reabsorption is decreased. The data also suggest that this effect is limited to juxtamedullary nephrons and is probably localized to the thin ascending limb of the loop of Henle.

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