1. The present study was designed to evaluate the effect of acute fall in plasma osmolality in three models of acute tubular necrosis in rats: (a) glycerol, (b) arterial clamping and (c) mercuric chloride.
2. Plasma osmolality was reduced by a water loading during a mild anaesthesia from 305 ± 7 to 270 ± 12 mosmol/kg of water (P<0.01).
3. In the ischaemic models of acute tubular necrosis (glycerol and arterial clamping), during the first 24 h in rats with reduced plasma osmolality, the respective creatinine clearance rates (CCR), 0.04 ± 0.02 and 0.06 ± 0.04 ml/min, were strikingly lower than those in rats with normal osmolality, 0.21 ± 0.03 and 0.26 ± 0.06 ml/min (P<0.001) respectively. The control CCR were 0.65 ± 0.07 and 0.62 ± 0.07 ml/min respectively.
4. During the second day after induction of ischaemic (glycerol and arterial clamping) acute tubular necrosis, rats with reduced plasma osmolality exhibited a similar worsening in CCR as on the first day, when compared with that in rats with normal osmolality.
5. In rats with acute tubular necrosis induced with mercuric chloride reduction in plasma osmolality did not aggravate the severity of renal failure.
6. These results show that acute fall in plasma osmolality worsens the renal failure in the ischaemic but not in the nephrotoxic models of acute tubular necrosis.