EVALUATION OF L-ARGININE/NITRIC OXIDE METABOLIC PATHWAY IN ERYTHROCYTES IN RELATION WITH OXIDATIVE STRESS: FOCUS ON DIFFERENT CARDIOVASCULAR DISEASES

Background: A decreased nitric oxide (NO) bioavailability and an increased oxidative stress play a pivotal role in different cardiovascular pathologies. Recent studies have shown that red blood cells (RBCs) participate in NO formation in the bloodstream. Aim: The aim of this study was to assess the L-arginine (Arg)/NO pathway and the oxidative stress status in RBCs and in plasma of patients with microvascular angina (MVA), investigating similarities and differences with respect to coronary artery disease (CAD) patients or healthy controls (Ctrl). Materials and Methods: Analytes involved in Arg/NO pathway and the ratio between the oxidized and the reduced forms of glutathione, as index of oxidative stress, were measured by liquid-chromatography tandem mass spectrometry (LC-MS/MS). The arginase and the NO synthase (NOS) expression were assessed by immunofluorescence staining. NOS activity was evaluated by ex-vivo experiments through the conversion of L-[15N2]arginine to L-[15N]citrulline. Results: Both MVA and CAD patients showed alterations in the ability of RBCs to produce NO, based on an increase of NO synthesis inhibitors, parallel to that found in plasma, a reduction of NOS expression and activity and an increased arginase expression. When summary scores of NO synthesis and of oxidative stress were computed, both patient groups were associated with a positive oxidative score and a negative NO score, with the CAD group located in a more extreme position with respect to Ctrl. Conclusions: This finding points out to an impairment of the capacity of RBCs to produce NO in pathological conditions characterized by alteration at the microvascular bed with/without no significant coronary stenosis.