REDUCED RENAL MEDULLARY WATER CHANNEL EXPRESSION IN PUROMYCIN AMINONUCLEOSIDE-INDUCED NEPHROTIC SYNDROME

The aquaporins are molecular water channels that mediate transcellular water transport across water-permeable epithelia. To investigate the cause of the concentrating defect in the nephrotic syndrome, immunoblo tting using membrane fractions from inner medulla was utilized to asse ss the level of expression of four aquaporin water channels in vehicle -treated versus puromycin aminonucleoside (PAN)-treated rats. Scanning electron microscopy demonstrating loss of glomerular foot processes a nd measurements of urinary protein excretion confirmed the efficacy of the PAN treatment. In rats receiving PAN, there was an increase in pl asma vasopressin, without a change in plasma sodium concentration. Inn er medullary tissue hypertonicity was sustained in PAN-treated rats wh ile the urinary osmolality was low, pointing to defective osmotic equi libration across the collecting ducts in PAN-nephrosis. Among collecti ng duct aquaporins, there was an 87% decrease in aquaporin-2 expressio n and a 70% decrease in aquaporin-3 expression in the inner medulla, w hereas aquaporin-4 expression was unaltered. Transmission electron mic roscopy of the inner medullary collecting ducts of PAN-treated rats sh owed normal-appearing cells. Thus, PAN-nephrosis is associated with an extensive downregulation of collecting duct water channel expression despite increased circulating vasopressin, providing an explanation fo r the concentrating defect associated with the nephrotic syndrome.