Direct effect of erythropoietin on rat vascular smooth-muscle cell via a putative erythropoietin receptor

BACKGROUND.: The treatment of uraemic patients with recombinant human erythropoietin(rHuEpo) often leads to an increase in blood pressure. Indirectand direct effects of the hormone are probably involved. Weexplored the possibility of a direct action on the vascularsmooth muscle cell (VSMC). METHODS.: Rat VSMC were isolated from aortas of spontaneously hypertensiverats (SHR) and normotensive control rats (WKY) and maintainedin culture. They were exposed to rHuEpo under various experimental conditions, and cells proliferative index was measuredby [³H]-thymidine incorporation. Binding studies and Northernblots were performed in an attempt to identify a specific erythropoietinreceptor (EpoR). In the latter experiment, Epo-responsive RauscherReds cells (Reds cells) were used as a positive control formRNA EpoR expression. RESULTS.: VSMC growth index of SHR was enhanced up to 1.6-fold by rHuEpoconcentrations of 16 U/ml or more, in the presence of 1% fetalcalf serum. No such stimulation was observed in VSMC of WKY.Binding studies with radiolabelled rHuEpo showed either extremelylow or no specific binding of radio-labelled rHuEpo by VSMC.However, Northern blot analysis revealed the expression of EpoRmRNA in VSMC of either rat strain. CONCLUSION.: The present report provides preliminary evidence in favour ofa direct action of the hormone on vascular smooth muscle viaa specific EpoR.