title: Essential role of bone marrow for microvascular endothelial and metabolic functions in mice.
abstract: BACKGROUND
  We have previously demonstrated that the importance of endothelium-derived hyperpolarizing factor (EDHF) increases as the vessel size decreases and that endothelium-derived hydrogen peroxide (H(2)O(2)) is an EDHF in animals and humans, for which endothelial nitric oxide synthase (eNOS) is the major source. Recent studies have suggested the important role of the bone marrow (BM) in modulating cardiovascular and metabolic functions.
  
  
  OBJECTIVE
  We aimed to examine whether BM plays a role in modulating microvascular endothelial and metabolic functions in mice, and if so, to elucidate the mechanisms involved.
  
  
  RESULTS
  Male eNOS(-/-) mice were transplanted with BM cells from wild-type (WT) or eNOS(-/-) mice and were maintained for 6 weeks. Endothelium-dependent relaxations and hyperpolarizations of mesenteric arteries to acetylcholine were reduced in eNOS(-/-) mice and were markedly improved when transplanted with WT-BM but not with eNOS(-/-)-BM. The enhanced component of endothelium-dependent relaxations was abolished by catalase, indicating that the improved responses were mediated by H(2)O(2). In contrast, no such beneficial effect was noted in the aorta. Reduced plasma adiponectin levels and impaired glucose tolerance in eNOS(-/-) mice were also improved by WT-BM transplantation. Neuronal nitric oxide synthase (nNOS) in mesenteric arteries of eNOS(-/-) mice was significantly upregulated only when transplanted with WT-BM. Importantly, the beneficial effects of WT-BM transplantation were absent in eNOS(-/-)/adiponectin(-/-) or eNOS(-/-)/nNOS(-/-) mice.
  
  
  CONCLUSIONS
  These results provide the first evidence that BM plays an important role in modulating microvascular endothelial and metabolic functions, for which adiponectin and nNOS may be involved.
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Sota
authors.initials: S
authors.lastname: Nakajima
authors.forename: Junko
authors.initials: J
authors.lastname: Ohashi
authors.forename: Ayuko
authors.initials: A
authors.lastname: Sawada
authors.forename: Kazuki
authors.initials: K
authors.lastname: Noda
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fukumoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000378:metabolism; D001685:Biological Factors / Q000378:metabolism; D001794:Blood Pressure; D001835:Body Weight; D001853:Bone Marrow / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D060833:Cellular Microenvironment; D004305:Dose-Response Relationship, Drug; D050171:Dyslipidemias / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005434:Flow Cytometry; D018149:Glucose Intolerance / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D005951:Glucose Tolerance Test; D006861:Hydrogen Peroxide / Q000378:metabolism; D007150:Immunohistochemistry; D008055:Lipids / Q000097:blood; D008297:Male; D008564:Membrane Potentials; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D018183:Transplantation Chimera; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D000975:Antioxidants; D001685:Biological Factors; D008055:Lipids; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D006861:Hydrogen Peroxide; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496315:Nos3 protein, mouse