Objectives: 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). © 2010 American College of Cardiology Foundation.
Meyer, C., Heiss, C., Drexhage, C., Kehmeier, E. S., Balzer, J., Mühlfeld, A., … Rassaf, T. (2010). Hemodialysis-Induced Release of Hemoglobin Limits Nitric Oxide Bioavailability and Impairs Vascular Function. Journal of the American College of Cardiology, 55(5), 454–459. https://doi.org/10.1016/j.jacc.2009.07.068