title: Dose-response relationship between norepinephrine and erythropoiesis: evidence for a critical threshold.
abstract: BACKGROUND
  Severe traumatic injury elicits a neuroendocrine response that activates the sympathetic nervous system. Our previous work suggests that norepinephrine (NE) influences the bone marrow (BM) erythropoietic response. However, the dose-response relationship between NE and erythropoiesis remains unclear.
  
  
  METHODS
  Two days following chemical sympathectomy with 6-hydroxydopamine (6-OHDA) or injection with saline vehicle (SHAM), male Sprague-Dawley rats were infused continuously with either saline (NS) or increasing doses of NE for 5 d via osmotic pumps. Erythropoiesis was assessed by growth of erythroid progenitor colonies (BFU-E and CFU-E for early and late progenitors, respectively).
  
  
  RESULTS
  Following chemical sympathectomy with 6-OHDA, both BFU-E and CFU-E growth is inhibited (42%∗ and 43%∗ versus 100% SHAM, ∗P < 0.05). SHAM rats with continuous infusion of exogenous NE show a clear dose-response inhibition of both BFU-E and CFU-E colony growth. In the 6-OHDA rats, continuous infusion of NE restored BFU-E and CFU-E growth at 10(-8) g/h and 10(-9) g/h, respectively.
  
  
  CONCLUSIONS
  Erythroid precursor colony growth is inhibited in sympathectomized rats. In addition, supraphysiologic doses of exogenous NE inhibit normal erythropoiesis in a dose-dependent fashion. Following chemical sympathectomy with 6-OHDA, exogenous NE restores erythropoiesis in a narrow window. Therefore, NE has a complex interaction within the BM and the elevation of NE following traumatic injury impacts BM erythropoietic function.
authors.affiliation: Department of Surgery, Division of Trauma University of Medicine and Dentistry New Jersey (UMDNJ)- New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Penn
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Mohr
authors.forename: Salil G
authors.initials: SG
authors.lastname: Shah
authors.forename: Ziad C
authors.initials: ZC
authors.lastname: Sifri
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Kaiser
authors.forename: Pranela
authors.initials: P
authors.lastname: Rameshwar
authors.forename: David H
authors.initials: DH
authors.lastname: Livingston
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015672:Erythroid Precursor Cells / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016627:Oxidopamine; D009638:Norepinephrine