EFFECTS OF VARIOUS ANTI-PLATELET DRUGS AND A DEFIBRINATING AGENT ON EXPERIMENTAL GLOMERULONEPHRITIS IN RATS

Abstract

Two types of experimental GN [glomerulonephritis] induced by immunological procedures, Hyemann-type AlC[autologous immune complex]-GN and NTN [nephrotoxic serum nephritis], were treated with anticoagulant agents. Dipyridamole, aspirin, ticlopidine or batroxobin was administered either to rats with AlC-GN for 14-28 days or to NTN rats 2 days prior to injection with NTS [nephrotoxic serum] and 14-21 days thereafter. A significant decrease in the amount of urinary protein was observed only in rats treated with 12.5-50.0 mg/kg dipyridamole daily, whereas no significant decrease in proteinuria was observed in either AlC-GN or NTN rats treated with the other agents. Histopathologically, no improvement in the light microscopic and EM findings was noted in AlC-GN rats treated with these agents, even with dipyridamole. In NTN rats, light microscopic and EM study of the kidneys from rats sacrificed 30 and 60 min after NTS injection revealed that platelet aggregation and inflammatory changes in the glomeruli were remarkably reduced in rats pretreated with 56.4 mg/kg aspirin or 50.0 mg/kg triclopidine daily, but no differences in the renal lesions between rats treated with aspirin or ticlopidine and control animals were observed 2 wk after NTS injection. No histological improvement was observed in rats pretreated with dipyridamole. Evidently, the favorable effect of dipyridamole on proteinuria is not related to its antiplatelet activity and platelet aggregation is not essential to the development of renal lesions in rat AlC-GN and NTN.