Role of plasminogen activator inhibitor on nephrotoxic nephritis and its modulation by tumor necrosis factor.
To evaluate the suggested imbalance between coagulation and fibrinolysis in the development of glomerulonephritis, plasminogen activator inhibitor (PAI) activity was studied in the plasma of rats with nephrotoxic nephritis. PAI activity rose within 1 h of the injection of nephrotoxic globulin (NTG), peaked at 2 h and returned to the normal range within 24 h. PAI activity was dependent on the dose of NTG and increased significantly during passage through the kidney. PAI activity was also detected in the culture supernatant from isolated glomeruli with nephrotoxic nephritis. Intracapillary fibrin deposits were formed within 2 h; their numbers increased gradually over 24 h. Tumor necrosis factor (TNF) also induced a progressive increase in PAI activity in normal rats. The injection of TNF to rats with NTG synergistically accelerated both the increase in PAI activity and the prevalence of fibrin deposits. These results suggest that PAI may be released from the glomeruli affected by nephrotoxic nephritis and imply that PAI may play a role in the local coagulation in the capillaries of the nephritic kidneys, although this is probably not the only mechanism which explains the continued formation of the glomerular fibrin deposits.
Tomosugi
N
N
First Department of Internal Medicine, School of Medicine, Kanazawa University, Japan.
Wada
T
T
Naito
T
T
Takasawa
K
K
Yokoyama
H
H
Kida
H
H
Kobayashi
K
K
D000818:Animals; D001777:Blood Coagulation; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005342:Fibrinolysis; D005921:Glomerulonephritis / Q000097:blood* / Q000209:etiology / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D015849:Plasminogen Inactivators / Q000097:blood* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015849:Plasminogen Inactivators; D014409:Tumor Necrosis Factor-alpha; D005337:Fibrin