Transglomerular cationic macromolecular flux is mediated by a convection-binding mechanism.
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.
Whiteside
C I
CI
Department of Medicine, University of Toronto, Ontario, Canada.
Lumsden
C J
CJ
D000818:Animals; D001696:Biomechanical Phenomena; D002412:Cations / Q000378:metabolism*; D003911:Dextrans / Q000378:metabolism / Q000652:urine; D004285:Dogs; D066298:In Vitro Techniques; D007201:Indicator Dilution Techniques; D007678:Kidney Glomerulus / Q000378:metabolism*; D046911:Macromolecular Substances; D008297:Male; D008845:Microinjections; D008954:Models, Biological; D011479:Protamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D002412:Cations; D003911:Dextrans; D046911:Macromolecular Substances; D011479:Protamines