Nitric oxide inhibition enhances platelet aggregation in experimental anti-Thy-1 nephritis

H van Goor*, EWJA Albrecht, P Heeringa, PA Klok, MLC van der Horst, A de Jager-Krikken, WW Bakker, H Moshage

*Corresponding author for this work

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17 Citations (Scopus)

Abstract

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-l-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-l-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. (C) 2001 Elsevier Science.

Original languageEnglish
Pages (from-to)525-533
Number of pages9
JournalNitric oxide-Biology and chemistry
Volume5
Issue number6
DOIs
Publication statusPublished - Dec-2001

Keywords

  • IMMUNE-COMPLEX GLOMERULONEPHRITIS
  • ARTERIAL-HYPERTENSION
  • SYNTHASE
  • RAT
  • MECHANISMS
  • EXPRESSION
  • GLOMERULI
  • BLOCKADE
  • NITRATE
  • MODEL

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