Nephrology Dialysis Transplantation, Vol 14, Issue 3 597-603, Copyright © 1999 by Oxford University Press
E Kusano, T Akimoto, M Inoue, Y Masunaga, T Umino, S Ono, Y Ando, S Homma, S Muto, N Komatsu and Y Asano
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-1{beta}-induced NO and cGMP production as well as
inducible nitric oxide synthase (iNOS) in cultured rat VSMC.
Method. Nitric 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-1{beta}-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-1{beta}-induced iNOS mRNA expression, rHuEpo vehicle did not affect
IL-1{beta}-induced iNOS mRNA expression. Conclusion.
It is suggested that a pharmacological dose of rHuEpo inhibits
IL-1{beta}-induced NO and cGMP production as well as iNOS mRNA
expression, presumably via the Epo receptor.
Keywords: cGMP; erythropoietin; erythropoietin
receptor; interleukin-1{beta}; nitric oxide; nitric oxide synthase;
vascular smooth-muscle cells
ORIGINAL ARTICLES
Human recombinant erythropoietin inhibits interleukin-1{beta}-stimulated nitric oxide and cyclic guanosine monophosphate production in cultured rat vascular smooth-muscle cells
Department of Nephrology and Haematology, Jichi Medical School, Yakushiji 3311-1, Minamikawachi, Tochigi 329-0498, Japan; Corresponding author
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