The effect of heparin on glomerular coagulation induced in mice by cycloheximide and bacterial lipopolysaccharide.
The glomerular capillary coagulation in mice which follows challenge with cycloheximide and a submicrogram dose of endotoxin was shown to become fully established between 4 h and 6 h after challenge. Complete protection against the renal lesion was achieved by heparin treatment 4 h after challenge. The antifibrinolytic agent, tranexamic acid, given 4 h and 6 h after challenge, abolished this heparin-induced protection, but had no effect when given 6 h and 8 h after challenge. These findings suggest that heparin in some way delayed the onset of cycloheximide and endotoxin-induced irreversible coagulation in glomerular capillaries, and by so doing, allowed the development of local, protective, fibrinolytic activity. A relatively brief period of such fibrinolytic activity appeared to confer lasting protection against coagulation in glomerular capillaries. Appropriately timed treatment with hydrocortisone also abolished the heparin-initiated protection, and the evidence suggests that the steroid acts by inhibiting the development of local fibrinolytic activity.
Parry
E W
EW
Department of Human Anatomy and Cell Biology, University of Liverpool, U.K.
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D003513:Cycloheximide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D004731:Endotoxins / Q000494:pharmacology*; D005342:Fibrinolysis / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology* / Q000627:therapeutic use; D006854:Hydrocortisone / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D014148:Tranexamic Acid / Q000494:pharmacology
D004731:Endotoxins; D008070:Lipopolysaccharides; D014148:Tranexamic Acid; D006493:Heparin; D003513:Cycloheximide; D006854:Hydrocortisone