Recombinant erythropoietin treatment does not alter the blood pressure despite elevated haematological parameters in normotensive Wistar rats


Keywords:
Rats Blood doping Erythropoietin Hypertension Hematocrit Plethysmography
F. SULTAN
B.A. GANAIE
D.M. MIR
J.A. DAR
Abstract

Use of erythropoietin (EPO) is believed to be associated with adverse cardiovascular events, especially high blood pressure. Also, its illegal use in blood doping is thought to result in detrimental events both in humans and equines. To test this hypothesis, normal Wistar rats were treated with recombinant erythropoietin (rEPO @ 400 i.u/kg s.c) or normal saline one day apart for one week. Heart rate, systolic, diastolic, mean arterial pressure and blood count were determined. Rats were also observed for their behaviour during the study period. rEPO significantly (P<0.001) increased the erythrocyte count (RBC), haemoglobin (Hb), hematocrit (HCT) and platelet count (PLT) in comparison to control animals. Despite such an increase in hematocrit which in turn increases blood viscosity, the systemic blood pressure and heart rate did not differ between the groups. rEPO treatment did not cause any untoward behavioural change in animals. In conclusion, despite the profound effect on haematological parameters (especially hematocrit), rEPO was without any effect on blood pressure and heart rate and the hypothesis of short-term erythropoietin-induced alterations in cardiac parameters was not verified.

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References
Abraham, P.A. and Macres, M.G. 1991. Blood pressure in hemodialysis patients during amelioration of anaemia with erythropoietin. J. Am. Soc. Nephrol. 2: 927-9.
Bennett, C.L., Silver, S.M., Djulbegovic, B., Samaras, A.T., Blau C.A., Gleason, K.J., Barnato, S.E., Elverman, K.M., Courtney, D.M., McKoy, J.M, Edwards, B.J, Tigue, C.C., Raisch, D.W., Yarnold, P.R., Dorr, D.A., Kuzel, T.M., Tallman, M.S., Trifilio, S.M., West, D.P., Lai, S.Y. and Henke, M. 2008. Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anaemia. JAMA. 299: 914-24.
Cowgill L.D., James K.M., Levy J.K, et al. 1998. Use of recombinant human erythropoietin for the management of anaemia in dogs and cats with renal failure. J Am Vet Med Assoc. 212:521–528.
Eschbach, J.W., Abdulhadi, M.H., Browne, J.K., Delano, B.G. and Downing, M.R. 1989. Recombinant human erythropoietin in anaemic patients with the end-stage renal disease. Results of phase III multicenter clinical trial. Ann. Intern. Med. 111: 992-1000.
Fishbane, S. and Nissenson, A.R. 2007. The new FDA label for erythropoietin treatment: How does it affect haemoglobin target? Kidney Intl. 72: 806–813.
Giger U. 1992. Erythropoietin and its clinical use. Compend Contin Educ
Pract Vet.14:25–34.
Heidenreich, S., Rahn, K.H. and Zidek, W. 1991. Direct vasopressor effect
of recombinant human erythropoietin on renal resistance vessels.
Kidney Intl. 39: 259-265.
Jelkmann, W. 1992. Erythropoietin: structure, control of production, and
function. Physiol. Rev. 72: 449 – 489.
Jelkmann, W. 2000. Use of recombinant human erythropoietin as an anti-anaemic and performance enhancing drug. Curr Pharmaceut Biotechnol. 1: 11–31.
Jelkmann, W. 2001. Beneficial and adverse effects of erythropoietin therapy. In: Peters, C., Schulz, T., Michnam, H., Druck, Eds. Biomedical Side Effects of Doping. Germany: Hansen, Bergisch Gladbach. 59–73.
Letcher R.L., Chien S., Pickering T.G., Sealey J.E. and Laragh J.H. 1981. Direct relationship between blood pressure and blood viscosity in normal and hypertensive subjects. Role of fibrinogen and concentration. Am J Med. 70:1195-1202.
Levy B.I., Schiffrin E.L., Mourad J.J., Agostini D., Vicaut E., Safar M.E. and Struijker-Boudier H.A. 2008. Impaired tissue perfusion: a pathology common to hypertension, obesity, and diabetes mellitus. Circulation. 118:968-76.
Lundby, C., Thomsen, J.J., Boushel, R., Koskolou, M., Warberg, J., Calbet, J.A. and Robach P. 2007. Erythropoietin treatment elevates haemoglobin
concentration by increasing red cell volume and depressing plasma volume. J Physiol. 578: 309–314.
Mikiciuk M.G., Polzin D.J. and Osborne C.A. 1990.The use of erythropoietin in chronic renal failure. Adv Small Animal Med Surg. 3:1–3.
Ni, Z., Wang, X.Q. and Vaziri, N.D. 1998. Nitric oxide metabolism in erythropoietin-induced hypertension: effect of calcium channel blockade. Hypertension.32: 724-9.
Pommering T.L. 2007. Erythropoietin and other blood-boosting methods. Pediatr Clin North Am. 54: 691–699.
Resch, B.E., Gaspar, R., Sonkodi, S. and Falkay, G. 2003. Vasoactive effects of erythropoietin on human placental blood vessels in vitro. Am J Obstet Gynecol. 188: 993-6
Steinbrook R. 2007. Erythropoietin, the FDA, and oncology. N Engl J Med 356: 2448–2451.
Sultan F., Singh T.U, Kumar T., Rungsung S., Rabha D.J., Vishwakarma A., Sukumaran S.V., Kandasamy A. and Parida S. 2017. Short-term exposure of erythropoietin impairs endothelial function through inhibition of nitric oxide production and eNOS mRNA expression in the rat pulmonary artery. Pharmacol Rep. 69: 658-665.
Toutain P.L. 2010. Veterinary medicines and competition animals: the question of medication versus doping control. Handb Exp Pharmacol. 199: 315-39.
Ungemach, F.R.1985. Doping control in race horses. Tierarztl Prax. 13:35-53.
Vogel J, Kiessling I, Heinicke K, Stallmach T, Ossent P, Vogel O, Aulmann M, Frietsch T, Schmid-Schonbein H, Kuschinsky W. and Gassmann M. 2003. Transgenic mice overexpressing erythropoietin adapt to excessive erythrocytosis by regulating blood viscosity. Blood. 102:2278-84.