Hemodialysis-induced release of hemoglobin limits nitric oxide bioavailability and impairs vascular function.
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).
Meyer
Christian
C
Division of Cardiology, Pulmonology and Vascular Medicine, University Hospital, Duesseldorf, Germany.
Heiss
Christian
C
Drexhage
Christine
C
Kehmeier
Eva S
ES
Balzer
Jan
J
Mühlfeld
Anja
A
Merx
Marc W
MW
Lauer
Thomas
T
Kühl
Harald
H
Floege
Jürgen
J
Kelm
Malte
M
Rassaf
Tienush
T
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
D006454:Hemoglobins; D009569:Nitric Oxide