title: Hemodialysis-induced release of hemoglobin limits nitric oxide bioavailability and impairs vascular function.
abstract: OBJECTIVE
  This study sought to characterize the impact of hemodialysis (HD)-induced release of hemoglobin on the bioavailability of nitric oxide (NO) and endothelial function.
  
  
  BACKGROUND
  Patients on chronic HD suffer from endothelial dysfunction and a massively increased risk for cardiovascular events. Although dialysis-dependent and -independent factors are discussed, the exact mechanisms are not fully understood.
  
  
  METHODS
  In 14 HD patients (56+/-15 years of age), endothelial function was determined by measuring flow-mediated dilation (FMD) of the brachial artery using high-resolution ultrasound before and after treatment. The NO consumption activity of plasma isolated from patients before and after hemodialysis was studied with an NO-sensitive electrode.
  
  
  RESULTS
  HD impaired FMD (3.5+/-2.6% to 1.7+/-1.4%, p=0.04) without affecting brachial artery diameter (4.7+/-0.6 mm vs. 4.4+/-0.9 mm, p=0.27). This was accompanied by an increase in cell-free plasma hemoglobin (196+/-43 mg/l to 285+/-109 mg/l, p=0.01), which led to a decrease in the bioavailability of free NO by more than 70%. Oxidation of the released plasma ferrous hemoglobin prevented the consumption of NO. The amount of decompartmentalized hemoglobin after HD correlated inversely with the change in FMD (r=-0.65, p=0.041).
  
  
  CONCLUSIONS
  Our data support a role of HD-induced release of hemoglobin in the pathogenesis of endothelial dysfunction in patients with end-stage renal disease. Approaches that oxidize free plasma hemoglobin may restore NO bioavailability and may have potential beneficial effects on vascular function. (Influence of Hemodialysis on Endothel-Depending Dilatation of Peripheral Arteries; NCT00764192).
authors.affiliation: Division of Cardiology, Pulmonology and Vascular Medicine, University Hospital, Duesseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Meyer
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.forename: Christine
authors.initials: C
authors.lastname: Drexhage
authors.forename: Eva S
authors.initials: ES
authors.lastname: Kehmeier
authors.forename: Jan
authors.initials: J
authors.lastname: Balzer
authors.forename: Anja
authors.initials: A
authors.lastname: Mühlfeld
authors.forename: Marc W
authors.initials: MW
authors.lastname: Merx
authors.forename: Thomas
authors.initials: T
authors.lastname: Lauer
authors.forename: Harald
authors.initials: H
authors.lastname: Kühl
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
authors.forename: Tienush
authors.initials: T
authors.lastname: Rassaf
mesh_terms: D000328:Adult; D000368:Aged; D001916:Brachial Artery / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000209:etiology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006461:Hemolysis; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D006435:Renal Dialysis / Q000009:adverse effects*; D014664:Vasodilation
chemical_list: D006454:Hemoglobins; D009569:Nitric Oxide