Dose-Response Relationship between Norepinephrine and Erythropoiesis: Evidence for a Critical Threshold

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 remai...

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Published in:The Journal of surgical research 2010-10, Vol.163 (2), p.e85-e90
Main Authors: Penn, Angela, M.D, Mohr, Alicia M., M.D, Shah, Salil G., M.D, Sifri, Ziad C., M.D, Kaiser, Vicki L., Ph.D, Rameshwar, Pranela, Ph.D, Livingston, David H., M.D
Format: Article
Language:English
Subjects:
6-hydroxydopamine
Animals
BFU-E
bone marrow
catecholamine
Cells, Cultured
CFU-E
chemical sympathectomy
Dose-Response Relationship, Drug
Erythroid Precursor Cells - drug effects
Erythropoiesis - drug effects
Male
Norepinephrine - pharmacology
Oxidopamine - pharmacology
Rats
Rats, Sprague-Dawley
Surgery
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Summary: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. Materials and 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%∗ versu s 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.
ISSN:0022-4804
1095-8673
DOI:10.1016/j.jss.2010.03.051