A micropuncture and renal clearance study in the rat of the urinary excretion of heparin, chondroitin sulfate and metabolic breakdown products of connective tissue proteoglycans

Abstract

Commercial heparin and acid glycosaminoglycans (AGAG) prepared from normal female human urine were tritiated catalytically in aqueous solution. Nasal septal chondroitin sulfate was tritiated by NaB3H4 reduction of the aldehydes produced by very limited periodate oxidation. The refined products were characterized by electrophoresis and biochemical analysis. The tritiated products were infused into Munich-Wistar rats, and their kidney clearances were measured and compared with that of inulin. The passage of heparin and chondroitin sulfate at the glomerulus was restricted, as shown by the ratios of their concentrations in Bowman's space fluid and plasma. Comparison with whole kidney urine/plasma ratios indicated that some tubular reabsorption also occurred. The low whole kidney clearance of AGAG from normal female human urine probably also resulted from restricted glomerular passage and tubular reabsorption. The low whole kidney clearances, primarily caused by restricted transglomerular movement, are discussed on the bases of (a) the molecular sizes and shapes of the AGAG, (b) an electrostatic barrier at the basement membrane and (c) binding of AGAG to plasma colloids, thus reducing plasma levels of free AGAG. The implications of these findings in (a) heparin therapy and (b) urinalysis of disorders of connective tissue metabolism are discussed.