title: Nitric oxide scavenging by red blood cell microparticles and cell-free hemoglobin as a mechanism for the red cell storage lesion.
abstract: BACKGROUND
  Intravascular red cell hemolysis impairs nitric oxide (NO)-redox homeostasis, producing endothelial dysfunction, platelet activation, and vasculopathy. Red blood cell storage under standard conditions results in reduced integrity of the erythrocyte membrane, with formation of exocytic microvesicles or microparticles and hemolysis, which we hypothesized could impair vascular function and contribute to the putative storage lesion of banked blood.
  
  
  RESULTS
  We now find that storage of human red blood cells under standard blood banking conditions results in the accumulation of cell-free and microparticle-encapsulated hemoglobin, which, despite 39 days of storage, remains in the reduced ferrous oxyhemoglobin redox state and stoichiometrically reacts with and scavenges the vasodilator NO. Using stopped-flow spectroscopy and laser-triggered NO release from a caged NO compound, we found that both free hemoglobin and microparticles react with NO about 1000 times faster than with intact erythrocytes. In complementary in vivo studies, we show that hemoglobin, even at concentrations below 10 μmol/L (in heme), produces potent vasoconstriction when infused into the rat circulation, whereas controlled infusions of methemoglobin and cyanomethemoglobin, which do not consume NO, have substantially reduced vasoconstrictor effects. Infusion of the plasma from stored human red blood cell units into the rat circulation produces significant vasoconstriction related to the magnitude of storage-related hemolysis.
  
  
  CONCLUSIONS
  The results of these studies suggest new mechanisms for endothelial injury and impaired vascular function associated with the most fundamental of storage lesions, hemolysis.
authors: Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors: Chenell
authors: C
authors: Donadee
authors: Nicolaas J H
authors: NJ
authors: Raat
authors: Tamir
authors: T
authors: Kanias
authors: Jesús
authors: J
authors: Tejero
authors: Janet S
authors: JS
authors: Lee
authors: Eric E
authors: EE
authors: Kelley
authors: Xuejun
authors: X
authors: Zhao
authors: Chen
authors: C
authors: Liu
authors: Hannah
authors: H
authors: Reynolds
authors: Ivan
authors: I
authors: Azarov
authors: Sheila
authors: S
authors: Frizzell
authors: E Michael
authors: EM
authors: Meyer
authors: Albert D
authors: AD
authors: Donnenberg
authors: Lirong
authors: L
authors: Qu
authors: Darrel
authors: D
authors: Triulzi
authors: Daniel B
authors: DB
authors: Kim-Shapiro
authors: Mark T
authors: MT
authors: Gladwin
mesh_terms: D000818:Animals; D001771:Blood Banks; D001793:Blood Preservation; D055252:Cell-Derived Microparticles / Q000737:chemistry*; D004912:Erythrocytes / Q000737:chemistry* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000737:chemistry*; D006454:Hemoglobins / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008706:Methemoglobin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D009569:Nitric Oxide / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D016166:Free Radical Scavengers; D006454:Hemoglobins; D014662:Vasoconstrictor Agents; C007169:cyanomethemoglobin; D009569:Nitric Oxide; D008706:Methemoglobin