Previous reports have shown a direct effect of erythropoietin (Epo) on vascular smooth muscle cells (VSMCs). Our aim was to assess expression of the Epo receptor (EpoR) on VSMCs and to study the activation of two major signaling cascades activated by Epo, namely JAK2/STAT5 and MAPK pathways. All experiments were performed in parallel using the Epo-responsive UT7 cell line. From semiquantitative RT-PCR experiments, VSMCs were estimated to express similar to 30-fold less EpoR mRNA than UT7 cells. Epo-induced phosphorylation of proteins involved in the EpoR/JAK2/STAT5 cascade could not be detected in VSMCs, even using pharmacological doses of Epo (250 IU/ml). In contrast, a strong activation of MAP kinase pathway was detected with as low as 10 IU/ml Epo. We suggest that MAPK activation reflects a physiologically relevant effect of Epo on VSMCs that may be correlated to cell proliferation. (C) zool Academic Press.