title: Sympathetic nervous system regulates bone marrow-derived cell egress through endothelial nitric oxide synthase activation: role in postischemic tissue remodeling.
abstract: OBJECTIVE
  Catecholamines have been shown to control bone marrow (BM)-derived cell egress, yet the cellular and molecular mechanisms involved in this effect and their subsequent participation to postischemic vessel growth are poorly understood.
  
  
  RESULTS
  Tyrosine hydroxylase mRNA levels, as well as dopamine (DA) and norepinephrine (NE) contents, were increased in the ischemic BM of mice with right femoral artery ligation. Angiographic score, capillary density, and arteriole number were markedly increased by treatments with DA (IP, 50 mg/kg, 5 days) or NE (IP, 2.5 mg/kg, 5 days). Using chimeric mice lethally irradiated and transplanted with BM-derived cells from green fluorescent protein mice, we showed that DA and NE enhanced by 70% (P<0.01) and 62% (P<0.001), respectively, the number of green fluorescent protein-positive BM-derived cells in ischemic tissue and promoted their ability to differentiate into cells with endothelial and inflammatory phenotypes. Similarly, both DA and NE increased the in vitro differentiation of cultured BM-derived cells into cells with endothelial phenotype. This increase was blunted by the nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester. DA and NE also upregulated the number of CD45-positive cells in blood 3 days after ischemia and that of macrophages in ischemic tissue 21 days after ischemia. Of interest, DA and NE increased BM endothelial nitric oxide synthase (eNOS) mRNA levels and were unable to promote BM-derived cell mobilization in chimeric eNOS-deficient mice lethally irradiated and transplanted with BM-derived cells from wild-type animals. Furthermore, administration of a β2 adrenergic agonist (clenbuterol, IP, 2 mg/kg, 5 days) and that of a dopaminergic D1/D5 receptor agonist (SKF-38393, IP, 2.5 mg/kg, 5 days) also enhanced BM-derived cell mobilization and subsequently postischemic vessel growth. CONCLUSION These results unravel, for the first time, a major role for the sympathetic nervous system in BM-derived cell egress through stromal eNOS activation.
authors.affiliation: Paris Cardiovascular Research Center, INSERM U970, Université Paris Descartes, 56 rue Leblanc, 75015 Paris, France.   jean-sebastien.silvestre@inserm.fr.
authors.forename: Alice
authors.initials: A
authors.lastname: Récalde
authors.forename: Adèle
authors.initials: A
authors.lastname: Richart
authors.forename: Coralie
authors.initials: C
authors.lastname: Guérin
authors.forename: Clément
authors.initials: C
authors.lastname: Cochain
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Zouggari
authors.forename: Kiave Ho Wang
authors.initials: KH
authors.lastname: Yin
authors.forename: José
authors.initials: J
authors.lastname: Vilar
authors.forename: Isabelle
authors.initials: I
authors.lastname: Drouet
authors.forename: Bernard
authors.initials: B
authors.lastname: Lévy
authors.forename: Odile
authors.initials: O
authors.lastname: Varoquaux
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Silvestre
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000201:enzymology* / Q000294:innervation; D001854:Bone Marrow Cells / Q000187:drug effects / Q000201:enzymology*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005263:Femoral Artery / Q000601:surgery; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006614:Hindlimb; D007511:Ischemia / Q000201:enzymology* / Q000503:physiopathology; D008026:Ligation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000098:blood supply*; D018919:Neovascularization, Physiologic; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D017154:Stromal Cells / Q000201:enzymology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D009638:Norepinephrine