A via L-arginina óxido nítrico, estresse oxidativo e ciclo da uréia na obesidade

• Autor(a) principal: Pereira, Natália Rodrigues
• Data de Publicação: 2011
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/12612
• topic: L-arginine; Nitric Oxide; Obesity; Cardiovascular Disease; Obesidade; Sistema cardiovascular; Arginina; Óxido nítrico; Distúrbios alimentares; Doença cardiovascular; CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA::FARMACOLOGIA CARDIORENAL

Obesity is a metabolic disorder of multifactorial etiology and high prevalence in Brazil, which can be defined as a body mass index (weight in kilograms divided by height in square meters) greater than or equal to 30 kg/m2, and that is independently 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 it acts as a cardiovascular protector modulating, for example, the relaxation of vascular smooth muscle and the platelet function. The aim of this thesis was to assess the L-arginine-NO pathway, as well as to investigate platelet function, oxidative stress, and the arginase activity in patients with obesity. The L-arginine transport, the production of cyclic guanosine monophosphate (cGMP), the activity and expression of NOS isoforms (eNOS and iNOS), the arginase activity, oxidative stress (production of reactive oxygen species - ROS; superoxide dismutase activity - SOD, and catalase activity), and platelet function were evaluated in platelets from patients with obesity. In erythrocytes, the L-arginine transport and the activity of NOS and arginase were investigated. Systemic levels of amino acids and inflammatory markers (fibrinogen and C-reactive protein) were also investigated. The results demonstrated that L-arginine influx via y+L system, NOS activity, and cGMP levels were decreased in platelets from obese subjects compared to healthy controls, whereas no difference was observed in arginase activity. In addition, the expression of NOS isoforms and platelet aggregation in platelets from patients with obesity was increased in relation to controls. In erythrocytes from these patients, there were a higher influx of L-arginine via y+ and y+L system, and NOS activity, and no difference in arginase function. The plasma concentration of L-arginine was not affected by obesity, whereas the concentration of inflammatory markers was significantly increased. The production of ROS and catalase activity in platelets were not altered in patients with obesity, whereas SOD activity was reduced. Thus, despite the increased NO production by erythrocytes, it is possible that the low platelet production of NO, in addition to a possible inflammatory state and oxidative stress, are contributing to the elevated platelet activity observed in obesity. These findings may contribute to a better understanding of the cardiovascular events seen in obesity