title: Effects of erythrocyte aging on nitric oxide and nitrite metabolism.
abstract: OBJECTIVE
  Recent studies have suggested that in addition to oxygen transport, red blood cells (RBC) are key regulators of vascular function by both inhibiting and promoting nitric oxide (NO)-mediated vasodilation. Most studies assume that RBC are homogenous, but, in fact, they comprise cells of differing morphology and biochemical composition which are dependent on their age, parameters that control NO reactions. We tested the hypothesis that distinct RBC populations will have differential effects on NO signaling.
  
  
  RESULTS
  Young and old RBC were separated by density gradient centrifugation. Consistent with previous reports, old RBC had decreased levels of surface N-acetyl neuraminic acid and increased oxygen binding affinities. Competition kinetic experiments showed that older RBCs scavenged NO∼2-fold faster compared with younger RBC, which translated to a more potent inhibition of both acetylcholine and NO-donor dependent vasodilation of isolated aortic rings. Moreover, nitrite oxidation kinetics was faster with older RBC compared with younger RBC; whereas no differences in nitrite-reduction kinetics were observed. This translated to increased inhibitory effect of older RBC to nitrite-dependent vasodilation under oxygenated and deoxygenated conditions. Finally, leukodepleted RBC storage also resulted in more dense RBC, which may contribute to the greater NO-inhibitory potential of stored RBC.
  
  
  METHODS
  These results suggest that a key element in vascular NO-homeostasis mechanisms is the distribution of RBC ages across the physiological spectrum (0-120 days) and suggest a novel mechanism for inhibited NO bioavailability in diseases which are characterized by a shift to an older RBC phenotype.
  
  
  CONCLUSIONS
  Older RBC inhibit NO bioavailability by increasing NO- and nitrite scavenging.
authors: Department of Pathology and Center for Free Radical Biology, University of Alabama at Birmingham , Birmingham, Alabama.
authors: Benjamin Y
authors: BY
authors: Owusu
authors: Ryan
authors: R
authors: Stapley
authors: Jaideep
authors: J
authors: Honavar
authors: Rakesh P
authors: RP
authors: Patel
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D004905:Erythrocyte Aging / Q000502:physiology*; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism*; D010084:Oxidation-Reduction; D011309:Preservation, Biological / Q000009:adverse effects; D051381:Rats; D015398:Signal Transduction; D014664:Vasodilation / Q000502:physiology
chemical_list: D009573:Nitrites; D009569:Nitric Oxide