Effects of a selective thromboxane A2 synthetase inhibitor on immune complex glomerulonephritis.
It has been reported that agents which block the prostaglandin system inhibit the development of glomerulonephritis. However, the mechanisms of these effects are not clear. We studied the effect of a selective thromboxane A2 (TxA2) synthetase inhibitor, 1-benzylimidazole (BIm), on the immune complex glomerulonephritis produced by bovine serum albumin (BSA) in New Zealand white rabbits. As the BSA nephritis developed, there was no change of creatinine (Cr), serum urea nitrogen (SUN), or creatinine clearance (Ccr), but urinary protein excretion increased almost 3-fold. Coagulation and fibrinolytic studies suggested a hypercoagulable state and increased fibrinolytic activity. Platelet aggregation showed the reduction of maximum aggregation induced by ADP and collagen. Histological examination by light microscopy, immunofluorescence, and electron microscopy revealed glomerular polymorphonuclear leukocyte (PMN) infiltration, mononuclear cell (MON) proliferation, and fibrin deposition. In 70% of the rabbits, IgG and C3 deposits were seen by immunofluorescence mainly in mesangial areas. The administration of BIm to BSA nephritis had no effects on Cr, SUN or Ccr, but it significantly lessened the proteinuria. The study of coagulation and fibrinolytic activity suggested a less hypercoagulable state, and more efficient fibrinolysis occurred than in the group without BIm. BIm tended to normalize platelet aggregation. It also lessened the histological PMN infiltration (p less than 0.05), MON proliferation (p less than 0.01), and fibrin deposition (p less than 0.05). These data suggest that TxA2 may play an important pathogenetic role in the development and progression of glomerulonephritis.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D003094:Collagen / Q000494:pharmacology; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D005342:Fibrinolysis / Q000187:drug effects; D005921:Glomerulonephritis / Q000097:blood / Q000209:etiology* / Q000473:pathology; D007093:Imidazoles / Q000494:pharmacology*; D007105:Immune Complex Diseases / Q000097:blood / Q000209:etiology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects; D011507:Proteinuria / Q000209:etiology; D011817:Rabbits; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D005338:Fibrin Fibrinogen Degradation Products; D007093:Imidazoles; C017062:1-benzylimidazole; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D003094:Collagen; D010088:Oxidoreductases; D013930:Thromboxane-A Synthase