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

van Goor, H., Albrecht, EWJA., Heeringa, P., Klok, PA., van der Horst, MLC., de Jager-Krikken, A., Bakker, WW. & Moshage, H., Dec-2001, In : Nitric oxide-Biology and chemistry. 5, 6, p. 525-533 9 p.

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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
Publication statusPublished - Dec-2001

    Keywords

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

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