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1. The relationship between osmolal clearance (CoSm) and the reabsorption of solute free water (PH,o) was examined during mannitol and hypertonic saline diureses in both normocalcaemic and hypercalcaemic rabbits.2. At high values for C,,, (2-4 ml/min) in normocalcaemic rabbits FH,O during saline diuresis exceeded that during mannitol diuresis as previously shown.3. Prolonged hypercalcaemia (72-96 h) reduced T ' H~O in both mannitol and saline diureses.4. Brief hypercalcaemia (18-24 h) abolished the increment in T'H,o normally seen during saline, as compared with mannitol diuresis. This impairment of T'H,o during saline diuresis occurred at a time after the start of hypercalcaemia when T'H,o during mannitol diuresis was still unaffected. 5. The results cannot be attributed to an effect of hypercalcaemia on membrane permeability to water, and are best explained by a reversible limitation of sodium transport in Henle's loop. This interpretation is supported by the fact that the hypercalcaemic rabbits excreted a greater percentage of the filtered sodium load than did the controls. . In studies on hypercalcaemic animals both maximal urinary osmolality and the reabsorption of solutefree water (T'H~O) during osmotic diuresis have been reduced, but the detailed mechanisms involved remain uncertain.We have studied urinary concentration in rabbits after short (18-24 h) periods of hypercalcaemia produced by infusion of calcium. Apart from maximal urinary osmolality, TH,O was measured during both mannitol and hypertonic saline diureses, as the latter solute normally results in higher values for T'H,o than does mannitol in the rabbit (Barraclough, Experiments were performed on male Californian rabbits weighing 2.0-3.5 kg. Nine rabbits were studied after the infusion of calcium salts for 18-24 h ('brief hypercalcaemia'), three rabbits were studied after calcium infusions for 72-96 h ('prolonged hypercalcaemia') and sixteen normocalcaemic rabbits were studied as controls.'Brief hypercalcaemia'. An intravenous catheter was placed in a femoral vein under light pentobarbitone anaesthesia and the animal placed in a restraining cage. Calcium was infused over 18-24 h in a solution containing 1000 units heparin per litre, 0.78 g Ca++/100 ml as calcium gluconate and 0.94 g Ca++/100 ml as calcium chloride. This solution was given by constant infusion pump at 0.047 ml/min, delivering Ca' + at 0-21-0.37 mg kg-' min-'. Rabbits 2, 3, 6, 7 and 12 were studied first under normal conditions and 3 4 weeks later after 'brief' calcium infusions. Rabbit 4 was also studied under both conditions but in the reverse order.'Prolonged hypercalcaemia'. The same solution used in the 'brief' calcium infusions was administered at 0 * 1 4 3 mg kg-' min-l of C a + + for 72-96 h. Of the three rabbits studied after these 'prolonged' infusions, rabbit 3 had previously been studied under normal conditions and also after 'brief hypercalcaemia'; rabbit 4 had been studied in the reverse order and rabbit 16 had been studied twice under normal conditions. Control rabb...

SUMMARY1. The relationship between osmolal clearance (Cosm) and the reabsorption of solute-free water by the kidney (T-H0) was examined during 10% mannitol and 2-3 % saline diuresis in normal and potassium-depleted rabbits.2. In normal rabbits at osmolal clearances close to 3 0 ml./min, TcH0 during mannitol diuresis was 0-87 + 0-06 ml./min and during saline diuresis 119 + 0 07 ml./min. The mean difference in Tc20 Of 0-32 + 0.05 ml./min was highly significant (P < 0*001).3. In one group of potassium-depleted rabbits with a reduction in maximal urinary concentration, Tc20 during both mannitol and saline diureses was reduced significantly below normal and the increment in TH20 normally seen during saline diuresis was abolished.4. In a second group of potassium-depleted rabbits maximal urinary concentration (1253 + 88 m-osmole/kg H20) was not significantly different from that in normal rabbits (1272 + 116 m-osmole/kg H20). In these animals, Tc20 at osmolal clearances close to 3 0 ml./min was not significantly different during mannitol diuresis (0-83 + 0 07 ml./min) from that in normal animals, whereas it was reduced significantly during saline diuresis (0.89 + 0-07 ml./min, P < 0.001) and the difference in Te20 normally seen between mannitol and saline diuresis was abolished.5. The inability to increase TH0 during saline diuresis above that achieved during mannitol appears to be the earliest manifestation of the concentrating defect associated with potassium depletion. It probably results from an impairment of sodium transport by the ascending limb of the loop of Henle. This is supported by the fact that potassium-depleted rabbits excreted a greater percentage of the filtered load of sodium than did normal controls.