Nitric oxide inhibition enhances platelet aggregation in experimental anti-Thy-1 nephritis.
In the present paper we studied the role of nitric oxide radicals (NO) on platelet aggregation, fibrinogen deposition, superoxide formation, peroxynitrite formation, hemodynamics, and leukocyte migration in the Thy-1 model of glomerulonephritis. To first study the baseline kinetics of these parameters, groups of anti-Thy-1-treated rats were sacrificed at 1 h, 4 h, 24 h, 3 days, 7 days, and 14 days and compared to controls. Urinary protein excretion was significantly elevated in Thy-1 nephritis at 3 and 7 days. Glomerular macrophages, PMNs, and superoxide anion-positive cells were significantly increased in Thy-1 nephritis. Nitrotyrosine immunoreactivity was absent during the entire study period. Glomerular platelet aggregation was significantly increased in anti-Thy-1 injected rats at 1 h, 4 h, 24 h, and 3 days. Glomerular fibrinogen deposition was significantly elevated at all time points. To elucidate the role of NO in this process, additional groups of anti-Thy-1-injected rats were treated with the NOS inhibitor l-NAME and studied at 24 h. Urinary protein excretion was significantly higher in l-NAME treated Thy-1 rats compared to nontreated Thy-1 rats. Plasma and urine nitrite/nitrate levels were significantly lower in l-NAME-treated Thy-1 rats compared to nontreated Thy-1 rats. Compared to nontreated Thy-1 rats, there were no differences in intraglomerular leukocyte accumulation after treatment with l-NAME. In contrast, we observed a marked increase in platelet aggregation following l-NAME treatment. From these data we conclude that the inflammatory infiltrate in Thy-1 nephritis develops independent of NO radical production, whereas NO radicals prevent the accumulation of platelet aggregates.
van Goor
H
H
Department of Pathology and Laboratory Medicine, University Hospital Groningen, Groningen, The Netherlands. h.van.goor@path.azg.nl
Albrecht
E W
EW
Heeringa
P
P
Klok
P A
PA
van der Horst
M L
ML
de Jager-Krikken
A
A
Bakker
W W
WW
Moshage
H
H
D000818:Animals; D001794:Blood Pressure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D007518:Isoantibodies / Q000276:immunology*; D007678:Kidney Glomerulus / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009393:Nephritis / Q000276:immunology / Q000503:physiopathology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010974:Platelet Aggregation / Q000502:physiology*; D011507:Proteinuria / Q000503:physiopathology; D051381:Rats; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D004791:Enzyme Inhibitors; D007518:Isoantibodies; C035678:anti-Thy antibody; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester