To test the hypothesis that neutralization of
polyanions of the glomerular filter in vivo will lead to loss of charge-dependent glomerular permselectivity, we have infused i.v. the polycation
hexadimethrine (HDM) into rats. Heavy
proteinuria resulted after a lag period of 30 to 50 min, and it resolved when the infusion was stopped. Concurrent administration of
heparin prevented the
proteinuria. Urinary
proteins were examined by immunoelectrophoresis, isoelectric focusing with immunofixation, and
sodium dodecylsulfate
polyacrylamide electrophoresis. The major
protein was rat
albumin, but there were also large quantities of intact rat
IgG. HDM was bound at known sites of
glomerular polyanion in the laminae rarae of the basement membrane and on the epithelial cell glycocalyx. Associated with this binding were reversible abnormalities of the epithelial cells similar to those seen during in vitro neutralization of
glomerular polyanion. Aside from proteinaceous tubular casts, no other histologic abnormality was noted. These studies provide direct evidence that neutralization of glomerular
polyanions in vivo results in heavy
proteinuria. The appearance of substantial quantities of rat
IgG in the urine implies that abnormalities of size as well as charge-dependent permselectivity occur, suggesting that the
polyanions of the glomerular filter may be important in maintaining its structure as well as its function.