title: Dietary nitrate supplementation improves revascularization in chronic ischemia.
abstract: BACKGROUND
  Revascularization is an adaptive repair mechanism that restores blood flow to undersupplied ischemic tissue. Nitric oxide plays an important role in this process. Whether dietary nitrate, serially reduced to nitrite by commensal bacteria in the oral cavity and subsequently to nitric oxide and other nitrogen oxides, enhances ischemia-induced remodeling of the vascular network is not known.
  
  
  RESULTS
  Mice were treated with either nitrate (1 g/L sodium nitrate in drinking water) or sodium chloride (control) for 14 days. At day 7, unilateral hind-limb surgery with excision of the left femoral artery was conducted. Blood flow was determined by laser Doppler. Capillary density, myoblast apoptosis, mobilization of CD34(+)/Flk-1(+), migration of bone marrow-derived CD31(+)/CD45(-), plasma S-nitrosothiols, nitrite, and skeletal tissue cGMP levels were assessed. Enhanced green fluorescence protein transgenic mice were used for bone marrow transplantation. Dietary nitrate increased plasma S-nitrosothiols and nitrite, enhanced revascularization, increased mobilization of CD34(+)/Flk-1(+) and migration of bone marrow-derived CD31(+)/CD45(-) cells to the site of ischemia, and attenuated apoptosis of potentially regenerative myoblasts in chronically ischemic tissue. The regenerative effects of nitrate treatment were abolished by eradication of the nitrate-reducing bacteria in the oral cavity through the use of an antiseptic mouthwash.
  
  
  CONCLUSIONS
  Long-term dietary nitrate supplementation may represent a novel nutrition-based strategy to enhance ischemia-induced revascularization.
authors.affiliation: Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany.
authors.forename: Ulrike B
authors.initials: UB
authors.lastname: Hendgen-Cotta
authors.forename: Peter
authors.initials: P
authors.lastname: Luedike
authors.forename: Matthias
authors.initials: M
authors.lastname: Totzeck
authors.forename: Martina
authors.initials: M
authors.lastname: Kropp
authors.forename: Andreas
authors.initials: A
authors.lastname: Schicho
authors.forename: Pia
authors.initials: P
authors.lastname: Stock
authors.forename: Christos
authors.initials: C
authors.lastname: Rammos
authors.forename: Michael
authors.initials: M
authors.lastname: Niessen
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.forename: Jon O
authors.initials: JO
authors.lastname: Lundberg
authors.forename: Eddie
authors.initials: E
authors.lastname: Weitzberg
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
authors.forename: Tienush
authors.initials: T
authors.lastname: Rassaf
mesh_terms: D000821:Animal Feed; D000818:Animals; D016026:Bone Marrow Transplantation; D002465:Cell Movement / Q000502:physiology; D002908:Chronic Disease; D006152:Cyclic GMP / Q000378:metabolism; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000178:diet therapy* / Q000503:physiopathology*; D017078:Laser-Doppler Flowmetry; D008026:Ligation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D032446:Myoblasts / Q000502:physiology; D009566:Nitrates / Q000097:blood / Q000494:pharmacology*; D009569:Nitric Oxide / Q000097:blood; D009573:Nitrites / Q000097:blood; D012038:Regeneration / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology; D026403:S-Nitrosothiols / Q000097:blood
chemical_list: D009566:Nitrates; D009573:Nitrites; D026403:S-Nitrosothiols; D049452:Green Fluorescent Proteins; D009569:Nitric Oxide; D006152:Cyclic GMP