AJP - Renal Physiology, Vol 256, Issue 5 882-F893, Copyright © 1989 by American Physiological Society
Transglomerular cationic macromolecular flux is mediated by a convection-binding mechanism
C. I. Whiteside and C. J. Lumsden
Department of Medicine, University of Toronto, Ontario, Canada.
Glomerular polyanion function was explored using charged and neutral
[3H]dextrans in the multiple indicator-dilution experiment. Anesthetized
dogs received an intrarenal bolus of 125I-labeled albumin (plasma
reference), [14C]inulin (glomerular reference) and [3H]dextran (test
solute), followed by rapid serial sampling of the renal venous and urine
outflows. Reduced urinary recovery of cationic diethylaminoethyl dextrans
(DEAE) [3H]dextrans [19.0- to 31.5-A Stokes-Einstein radius (SER)],
compared with neutral [3H]dextran indicated intrarenal binding reversed by
excess unlabeled cationic dextran. Tubular microperfusion with cationic
[3H]dextran confirmed a pretubular binding site (presumed glomerular). The
application of a computer-assisted mathematical model of convective flux
plus reversible binding revealed that binding affinity increased with
molecular size. In vitro high-affinity binding of the same cationic
[3H]dextrans to isolated rat glomeruli was also found to increase with
molecular size and was inhibited by protamine sulfate. Intrarenal
polycation perfusion with protamine sulfate (1.0-3.8 mg/g kidney) or
lysozyme (1.1-2.2 mg/g body wt) resulted in intraglomerular binding of
anionic [3H]dextran without increased proteinuria or altered glomerular
permselectivity to neutral [3H]dextrans less than or equal to 33.0-A SER.
Hence, transglomerular cationic solute flux is mediated by a
convection-binding mechanism that creates an effective polyvalent barrier.
