Mechanism of Increased Renal Sodium Excretion Following Mannitol Infusion in Man

Abstract

Mannitol, when given intravenously to normal human subjects or animals, shares with a number of other substances the property of promoting an increased rate of renal excretion of sodium, chloride, and water. The generally accepted hypothesis concerning the mechanism of this action is that mannitol exerts its effect directly on the renal tubules. The osmotic pressure of the mannitol within the tubular lumen is considered to interfere with the reabsorption of water. Sodium excretion is thought to be increased in the presence of the increased amounts of water in the tubule per unit time, either because reabsorption of sodium is limited by a maximum concentration difference for sodium which can be achieved between the tubular urine and the extracellular fluid (1)(2)(3) or because the contact of the sodium with the tubule cells is so brief that reabsorption is incomplete (4, 5). Evidence for a direct effect of mannitol on the renal excretion of salt and water is afforded by the experiments of Goodyer and Glenn (5). They injected large mannitol loads directly into one renal artery of dogs and produced prompt increases in salt and water excretion on the injected side. However another mechanism of action of mannitol in the intact animal is not excluded by these observations. Seldin and Tarail (6) have suggested that mannitol infusions may exert their effects outside the kidney by producing an expansion of extracellular volume and, when given in hypertonic solution, a contraction of intracellular volume, and thus indirectly altering some regulatory mechanism which increases the renal excretion of salt. This hypothesis has not thus far been excluded, and indeed was suggested as the probable mechanism of ac-1 Present address: Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carol'a tion of sodium chloride infusions in increasing renal sodium excretion by Green and Farah (7). They believe that the increased sodium intake influences sodium excretion primarily by establishing an osmotic pressure difference between extraand intracellular fluids.In most studies (1,4,6,8,9) hypertonic mannitol solutions (usually 25 per cent) have been injected. Such solutions would be expected, and have been calculated, to expand extracellular volume and contract intracellular volume. West, Kaplan, Fomon, and Rapoport (10) gave hypotonic mannitol solutions to hydrated dogs and found increased salt excretion. Here extracellular volume was expanded and although under such circumstances an absolute contraction of intracellular volume would appear unlikely, the calculated osmolarity of the plasma did rise during the mannitol infusion and therefore a relative decrease in intracellular water cannot be excluded.Goodyer and Seldin ( 11 ) gave hypertonic mannitol solutions to two subjects during quiet standing and found less increase in salt excretion than normally occurs; to one standing, hydrated subject they gave a small amount (one liter) of hypotonic mannitol and found no increase in salt excretion.2 Recent...

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