Monoamine oxidases contribute to endothelial dysfunction of the vascular access in hemodialysis patients

Abstract

OBJECTIVES Arteriovenous fistulas (AVF) are the 'lifeline' for patients with terminal end-stage renal disease (ESRD) on chronic hemodialysis. AVF maturation failure is a poorly understood process, and is partially caused by endothelial dysfunction due to oxidative stress. Monoamine Oxidases (MAOs) A and B were recently identified as novel sources of vascular oxidative stress. AIM To assess the contribution of MAOs to endothelial dysfunction in patients with ESDR with indication of hemodialysis. MATERIALS AND METHODS Fragments taken from brachial artery collaterals were harvested from ESRD patients during the surgical procedure that was applied in order to create the AVF in the cubital fossa. The effect of the irreversible MAO-A inhibitor clorgyline (10 µmol/L) and irreversible MAO-B inhibitor selegyline (10 µmol/L) on endothelialdependent relaxation (EDR) in response to cumulative doses of acetylcholine was studied in isolated phenylephrine-preconstricted rings in the presence of diclofenac (10µmol/L). H2O2 production was analyzed using ferrous oxidation xylenol orange assay. MAO expression was assessed by quantitative PCR. RESULTS We showed that both MAO isoforms are expressed in the brachial artery collaterals. Incubation with MAO inhibitors significantly improved EDR and attenuated H2O2 generation in the vascular segments. CONCLUSIONS MAO-related oxidative stress might contribute to the primary dysfunction/lack of maturation of the AVF and MAO inhibitors could improve vascular access maturation and longevity in dialysis patients

Keywords

• arteriovenous fistula
• MAO
• oxidative stress
• endothelial dysfunction.