Role of the liver and kidney in the desulphation of heparin in vivo.
Heparin radiolabelled with 125I was given intravenously to intact, bilaterally nephrectomised or completely hepatectomised rats in the presence and absence of 1 mg unlabelled heparin/kg. Plasma samples were collected and analysed by gel filtration chromatography and affinity chromatography on Polybrene-Sepharose, which binds sulphated glycosaminoglycans. Radiolabel in the plasma was associated with both intact heparin and fully desulphated macromolecular carbohydrate chains. Levels of intact heparin in plasma from control rats decreased with time at both doses with a concomitant increase in desulphated material. Livers accumulated the greatest amounts of radiolabel on a per organ basis. Hepatectomy both increased levels of radiolabel in plasma and decreased amounts of desulphated heparin produced, indicating that the liver was the major site of desulphation. Even after removal of the liver, the desulphated metabolite comprised approximately 15% of radiolabelled material at all times and doses, suggesting an additional site of GAG desulphation which may be the vascular endothelium. The kidneys contributed significantly to in vivo desulphation of heparin only at the high dose.
Wells
X E
XE
Heart Research Institute, Camperdown, New South Wales, Australia.
Dawes
J
J
D000818:Animals; D001711:Biotransformation; D002850:Chromatography, Gel; D006493:Heparin / Q000493:pharmacokinetics*; D006498:Hepatectomy; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D009392:Nephrectomy; D009609:Nitrous Oxide / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013455:Sulfur / Q000378:metabolism; D014018:Tissue Distribution
D013455:Sulfur; D006493:Heparin; D009609:Nitrous Oxide