Composition of Excreted Solutes in Experimental Diabetes Insipidus Mechanism of Urinary Dilution

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Abstract
Dogs with experimentally induced diabetes insipidus, allowed free access to water, were subjected to solute loading expts. Substances injected were mannitol, NaNO3, and Na ferrocyanide. Observations, before and after loading, included those of urine flow, osmolarity, composition of solutes in urine and plasma, and clearances. For comparative purposes, similar expts. were performed on normal dogs under standard hydropenic conditions. In all, 23 expts. covering 156 periods of urine collection were performed. During preliminary periods, diabetes insipidus dogs with free access to water excreted hypotonic urine (100-250 mOs./l.) at rates of flow of 1.5-5.5 cc./min. After loading, urinary osmolarity increased to levels of 200-400 mOs./l., while urine now attained a value as high as 35 cc./min. Flow-load data indicated that dogs with diabetes insipidus required twice the normal volume of urinary water for the excretion of a given solute load. With respect to the excretion of individual solutes, the urinary composition of exptl., was the same as that of normal hydropenic dogs. Consequently, for a given loading substance, the percentage make-up of dissolved constituents of the urine, (loading anion or nonelectrolyte, Na, Cl, K, and urea) was independent of the osomotic pressure of the urine, and dependent mainly, on the magnitude of the excreted load. Under the conditions of present expts., urea excretion was independent even of the chemical nature of the loading substance. Observed differences of clearances (mannitol, inulin, ferrocyanide, and PAH), and of plasma levels of loading substances, together with the similarity of urinary solute composition suggested an independence of the renal functions of solute transfer and hemodynamics. Data on solute composition and flow-load relations provide indirect evidence in support of the inference that excreted solutes are assembled at a locus in the renal tubule proximal to that of concn. or dilution of the urine. The corollary of such an inference is that the most distal region of the renal tubule would be a specialized organ of water transport. Consequently, it would reabsorb water to produce hypertonic, and secrete water into the lumen to produce hypotonic urine.