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. Indirect and direct effects of the hormone are probably involved. We explored the possibility of a direct action on the vascular smooth muscle cell (VSMC). Methods. Rat VSMC were isolated from aortas of spontaneously hypertensive rats (SHR) and normotensive control rats (WKY) and maintained in culture. They were exposed to rHuEpo under various experimental conditions, and cells proliferative index was measured by [H-3]-thymidine incorporation. Binding studies and Northern blots were performed in an attempt to identify a specific erythropoietin receptor (EpoR). In the latter experiment, Epo-responsive Rauscher Reds cells (Reds cells) were used as a positive control for mRNA EpoR expression. Results. VSMC growth index of SHR was enhanced up to 1.6-fold by rHuEpo concentrations of 16 U/ml or more, in the presence of 1% fetal calf serum. No such stimulation was observed in VSMC of WKY. Binding studies with radiolabelled rHuEpo showed either extremely low or no specific binding of radiolabelled rHuEpo by VSMC. However, Northern blot analysis revealed the expression of EpoR mRNA in VSMC of either rat strain. Conclusion. The present report provides preliminary evidence in favour of a direct action of the hormone on vascular smooth muscle via a specific EpoR.