Nephrology Dialysis Transplantation 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 [3H]-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.

[1]  M. Yanai,et al.  Recombinant human erythropoietin has no direct or strong vasoconstrictor effects in vivo and in vitro. , 1995, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[2]  M. Gassmann,et al.  Localization of specific erythropoietin binding sites in defined areas of the mouse brain. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[3]  R. Carlini,et al.  Recombinant human erythropoietin stimulates angiogenesis in vitro. , 1995, Kidney international.

[4]  G. Maschio,et al.  Erythropoietin and systemic hypertension. , 1995, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[5]  J. Zingraff,et al.  Does intravenous erythropoietin lead to an immediate, transient increase in arterial blood pressure in dialysis patients? , 1994, Nephron.

[6]  A. Wickrema,et al.  Distinct roles of erythropoietin, insulin-like growth factor I, and stem cell factor in the development of erythroid progenitor cells. , 1994, The Journal of clinical investigation.

[7]  M. Brier,et al.  Effect of erythropoietin on renal excretion of a sodium load , 1994, Clinical pharmacology and therapeutics.

[8]  A. Anagnostou,et al.  Erythropoietin receptor mRNA expression in human endothelial cells. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[9]  J. Gogusev,et al.  Effect of erythropoietin on DNA synthesis, proto-oncogene expression and phospholipase C activity in rat vascular smooth muscle cells. , 1994, Biochemical and biophysical research communications.

[10]  K. Eckardt.  Erythropoietin: oxygen-dependent control of erythropoiesis and its failure in renal disease. , 1994, Nephron.

[11]  S. Masuda,et al.  Functional erythropoietin receptor of the cells with neural characteristics. Comparison with receptor properties of erythroid cells. , 1993, The Journal of biological chemistry.

[12]  A. Dusso,et al.  Recombinant human erythropoietin (rHuEPO) increases endothelin-1 release by endothelial cells. , 1993, Kidney international.

[13]  T. Tabira,et al.  Trophic effect of erythropoietin and other hematopoietic factors on central cholinergic neurons in vitro and in vivo , 1993, Brain Research.

[14]  T. Ishimitsu,et al.  Genetic predisposition to hypertension facilitates blood pressure elevation in hemodialysis patients treated with erythropoietin. , 1993, The American journal of medicine.

[15]  M. Brier,et al.  Erythropoietin-induced antinatriuresis mediated by angiotensin II in perfused kidneys. , 1993, Journal of the American Society of Nephrology : JASN.

[16]  R. Carlini,et al.  Intravenous erythropoietin (rHuEPO) administration increases plasma endothelin and blood pressure in hemodialysis patients. , 1993, American journal of hypertension.

[17]  T. Ishimitsu,et al.  Direct vasopressor effects of erythropoietin in genetically hypertensive rats. , 1993, Life sciences.

[18]  W. Vainchenker,et al.  Granulocyte-macrophage colony-stimulating factor and erythropoietin act competitively to induce two different programs of differentiation in the human pluripotent cell line UT-7. , 1992, Blood.

[19]  G. Montini,et al.  Evidence for specific binding and stimulatory effects of recombinant human erythropoietin on isolated adult rat Leydig cells. , 1992, Acta endocrinologica.

[20]  N. Casadevall,et al.  Erythropoietin induces the tyrosine phosphorylation of its own receptor in human erythropoietin-responsive cells. , 1992, The Journal of biological chemistry.

[21]  D. Zhu,et al.  Protein kinase C and cell proliferation in spontaneously hypertensive rats. , 1992, Clinical and experimental hypertension. Part A, Theory and practice.

[22]  C. Tournamille,et al.  Cloning of the gene encoding the human erythropoietin receptor. , 1991, Blood.

[23]  A. Raine,et al.  Effects of erythropoietin on blood pressure. , 1991, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[24]  J. Spivak,et al.  Erythropoietin is both a mitogen and a survival factor. , 1991, Blood.

[25]  K. Rahn,et al.  Direct vasopressor effect of recombinant human erythropoietin on renal resistance vessels. , 1991, Kidney international.

[26]  Y. Ikawa,et al.  Characterization of murine erythropoietin receptor genes. , 1990, Journal of molecular biology.

[27]  A. Anagnostou,et al.  Erythropoietin has a mitogenic and positive chemotactic effect on endothelial cells. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[28]  J. Walls,et al.  Erythropoietin does not induce vasoconstriction directly in human subcutaneous resistance arterioles. , 1989, Nephron.

[29]  P. Mayeux,et al.  The erythropoietin receptor of rat erythroid progenitor lens. Characterization and affinity cross-linkage. , 1987, The Journal of biological chemistry.

[30]  Sanford,et al.  Binding and receptor-mediated endocytosis of erythropoietin in Friend virus-infected erythroid cells. , 1987, The Journal of biological chemistry.

[31]  J. Guénet,et al.  Number and organization of actin-related sequences in the mouse genome. , 1983, Journal of molecular biology.

[32]  L. Griensven,et al.  A new erythroid cell line induced by Rauscher murine leukaemia virus , 1978, Nature.

[33]  N. Blin,et al.  A general method for isolation of high molecular weight DNA from eukaryotes. , 1976, Nucleic acids research.

[34]  R. Ross.  The smooth muscle cell. II. Growth of smooth muscle in culture and formation of elastic fibers. , 1971 .