Mecanismos moleculares e celulares envolvidos na modulação da via L-arginina-óxido nítrico em pacientes com insuficiência renal crônica em hemodiálise

Abstract

Chronic renal failure (CRF) is a clinical syndrome with high prevalence in Brazil, which can be defined by a progressive and irreversible decline in renal function (glomerular, tubular and endocrine). It is associated with a high risk of cardiovascular morbidity and mortality due to atherothrombotic events. Nitric oxide (NO), a small gaseous molecule, is produced through the conversion of the cationic amino acid L-arginine to L-citrulline and NO in a reaction catalyzed by a family of enzymes called NO synthases (NOS) and modulates the relaxation of vascular smooth muscle, immune system and the platelet function. The objective of this dissertation was to evaluate L-arginine-NO pathway, as well as to investigate platelet function and oxidative stress in patients with CRF on hemodialysis (HD). L-arginine transport, the activity and expression of NOS isoforms (eNOS and iNOS) and L-arginine levels in neutrophils, systemic oxidative status (Protein oxidation and lipid peroxidation; glutathione peroxidase-GPx, and catalase activities), the effects of neutrophils in platelet function and oxidative burst were measured in patients with CRF on HD. Fifteen patients with CRF on maintenance HD and fifteen healthy controls matched by age were included in this study. Our results showed reduced NOS activity in neutrophils from CRF patients on HD compared to controls. This happened in the presence of normal concentration of L-arginine and its transport, and inaltered expression of endothelial and inducible NOS. Platelet aggregation was diminished after incubation for 5 and 30 minutes with neutrophils from patients with CRF and controls without difference between the groups. Systemic oxidative stress markers evaluated by protein oxidation and lipid peroxidation; anti-oxidant enzymes GPx, and catalase activities were not modified in serum by CRF. Another analysis evaluated the production of superoxide in neutrophils stimulated, and there was no difference in neutrophils by CRF. Our results demonstrared reduced NO production in neutrophils from CRF patients on hemodialysis, indenpedent of L-arginine bioavailability, and the importance of neutrophils in platelet function. Therefore, there may be a link between this syndrome and cardiovascular disease.