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

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 patient

CONTRIBUTION OF MONOAMINE OXIDASES TO VASCULAR OXIDATIVE STRESS IN PATIENTS WITH END-STAGE RENAL DISEASE REQUIRING HEMODIALYSIS

Arteriovenous fistula (AVF) is the 'life line' for patients with end-stage renal disease (ESRD) undergoing hemodialysis. AVF maturation failure is a poorly understood process, one of the contributors being endothelial dysfunction due to oxidative stress. Monoamine oxidases (MAOs) A and B were recently identified as novel sources of vascular oxidative stress. The aim of the present study was to assess the contribution of MAOs to the endothelial dysfunction in patients with ESDR with indication of hemodialysis. Fragments of brachial artery collaterals were harvested from ESRD patients during the surgical procedure aimed at creating the vascular access in the cubital fossa. The effect of increasing concentrations (10, 30, 100 Âľmol/L) of the irreversible MAO-A inhibitor, clorgyline and MAO-B inhibitor, selegyline, respectively on endothelial-dependent relaxation (EDR) in response to cumulative doses of acetylcholine was studied in isolated phenylephrine-preconstricted vascular rings. Hydrogen peroxide (H2O2) production was assessed using ferrous oxidation xylenol orange assay. We showed that incubation of brachial rings with MAO inhibitors significantly improved EDR and attenuated H2O2 generation in patients with ESRD. MAO-related oxidative stress might contribute to the primary dysfunction/non-maturation of the AV fistula and MAO inhibitors could improve maturation and long-term patency of the vascular access in dialysis patients.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author