Journal Article

Human recombinant erythropoietin inhibits interleukin-1beta-stimulated nitric oxide and cyclic guanosine monophosphate production in cultured rat vascular smooth-muscle cells.

E Kusano, T Akimoto, M Inoue, Y Masunaga, T Umino, S Ono, Y Ando, S Homma, S Muto, N Komatsu and Y Asano

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 14, issue 3, pages 597-603
Published in print March 1999 | ISSN: 0931-0509
Published online March 1999 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/14.3.597
Human recombinant erythropoietin inhibits interleukin-1beta-stimulated nitric oxide and cyclic guanosine monophosphate production in cultured rat vascular smooth-muscle cells.

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BACKGROUND: Recently rat vascular smooth-muscle cells (VSMC) have been shown to possess Epo receptor, and respond to various cytokines for producing nitric oxide (NO). In the present study we examined the effect of pharmacological dose of human recombinant erythropoietin (rHuEpo) on the IL-1beta-induced NO and cGMP production as well as inducible nitric oxide synthase (iNOS) in cultured rat VSMC. METHODS: Nitrite, a stable metabolite of NO, and intracellular cGMP contents were assayed by Griess method and enzyme immunoassay. iNOS mRNA expression was analysed by Northern blotting. RESULTS: RHuEpo inhibited IL-1beta-induced nitrite production in a dose- and time-dependent manner with concomitant changes of intracellular cGMP contents. On the other hand, rHuEpo did not inhibit atrial natriuretic peptide- (ANP) or sodium nitroprusside (SNP)-induced nitrite and cGMP production at all. While rHuEpo inhibited IL-1beta-induced iNOS mRNA expression, rHuEpo vehicle did not affect IL-1beta-induced iNOS mRNA expression. CONCLUSIONS: It is suggested that a pharmacological dose of rHuEpo inhibits IL-1beta-induced NO and cGMP production as well as iNOS mRNA expression, presumably via the Epo receptor.

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Subjects: Nephrology

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