Both acute and prolonged administration of EPO reduce cerebral and systemic vascular conductance in humans

Administration of erythropoietin (EPO) has been linked to cerebrovascular events. EPO reduces vascular conductance, possibly because of the increase in hematocrit. Whether EPO in itself affects the vasculature remains unknown; here it was evaluated in healthy males by determining systemic and cerebrovascular variables following acute (30,000 IU/d for 3 d; n = 8) and chronic (5000 IU/week for 13 wk; n = 8) administration of EPO, while the responsiveness of the vasculature was challenged during cycling exercise, with and without hypoxia. Prolonged administration of EPO increased hematocrit from 42.5 +/- 3.7 to 47.6 +/- 4.1% (P <0.01), whereas hematocrit was unaffected following acute EPO administration. Yet, the two EPO regimes increased arterial pressure similarly (by 8 +/- 4 and 7 +/- 3 mmHg, respectively; P=0.01) through reduced vascular conductance (by 7 +/- 3 and 5 +/- 2%; P <0.05). Also, both EPO regimes widened the arterial-to-jugular O-2 differences at rest as well as during normoxic and hypoxic exercise (P <0.01), which indicated reduced cerebral blood flow despite preserved dynamic cerebral autoregulation, and an increase in middle cerebral artery mean blood flow velocity (P <0.05), therefore, reflected vasoconstriction. Thus, administration of EPO to healthy humans lowers systemic and cerebral conductance independent of its effect on hematocrit.-Rasmussen, P., Kim, Y. S., Krogh-Madsen, R., Lundby, C., Olsen, N. V., Secher, N. H., van Lieshout, J. J. Both acute and prolonged administration of EPO reduce cerebral and systemic vascular conductance in humans. FASEB J. 26, 1343-1348 (2012). www.fasebj.org