To explore the mechanism of Cd nephrotoxicity, CdCl2 was subcutaneously injected to rats, at 3 mg Cd/kg body weight once a day, for 8 d. In the liver, Cd bound to metallothioneins (MTs-Cd) rose from d 1 after the initiation of CdCl2 administration, and reached a plateau after the administration ceased. In the plasma, MTs-Cd rose from d 4, peaked on d 8, and gradually fell thereafter. In the kidneys, leucine aminopeptidase (LAP) and N-acetyl beta-D-glucosaminidase (NAG) fell during d 6-20, and Cd bound to cellular membranes (Mem-Cd) rose from d 1 and reached a plateau during d 6-20. The Mem-Cd levels were significantly correlated with the reduction in the LAP and NAG activity; the values of MTs-Cd plus Mem-Cd were almost equivalent to those of total Cd. These findings showed that the hepatic synthesis of MTs-Cd occurred followed by its release into plasma; the extent of renal injury was aggravated as the plasma level of MTs-Cd rose; and a greater part of the renal Cd distributed intracellularly as the MTs-binding form, while the residual Cd distributed as the cellular membrane-binding form. Also, it was suggested that Cd that occurred as the cellular membrane- binding form in the kidneys was involved in manifestation of renal injury.

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To compare proteinuric potentials among angiotensin II (ANG II) and its fragments, [des-Asp1]-angiotensin II (ANG III) and [des-Asp1, des-Arg2]-angiotensin II (ANG IV), the peptide was intravenously infused for 30 min at doses of 0.015, 0.05, 0.15, 0.45 and 1.45 nmol/kg body weight/min. The infusion of ANG II and ANG III increased the fractional clearance of albumin in a dose-dependent manner: most extensively for ANG II, and moderately for ANG III. In contrast, the infusion of ANG IV hardly showed any proteinuric action, even at the maximal dose of 1.45 nmol/kg body weight/min. These results denoted that the cleaving of the N-terminal aspartic acid1 from ANG II weakened the proteinuric action in the glomeruli, and the further cleaving of the N-terminal arginine from ANG III led to a complete loss of proteinuric action in the glomeruli.