title: Both acute and prolonged administration of EPO reduce cerebral and systemic vascular conductance in humans.
abstract: 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.
authors.affiliation: University of Zurich, Building 23, Winterthurerstrasse 190, CH8057, Zurich, Switzerland. peter@prec.dk
authors.forename: Peter
authors.initials: P
authors.lastname: Rasmussen
authors.forename: Yu-Sok
authors.initials: YS
authors.lastname: Kim
authors.forename: Rikke
authors.initials: R
authors.lastname: Krogh-Madsen
authors.forename: Carsten
authors.initials: C
authors.lastname: Lundby
authors.forename: Niels V
authors.initials: NV
authors.lastname: Olsen
authors.forename: Niels H
authors.initials: NH
authors.lastname: Secher
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: van Lieshout
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology*; D015444:Exercise; D006400:Hematocrit; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D055815:Young Adult
chemical_list: D004921:Erythropoietin; D010100:Oxygen