Doenças cardiovasculares em pacientes bipolares: uma investigação da biodisponibilidade do óxido nítrico

• Autor(a) principal: Souza, Paula Fontoura Coelho de
• Data de Publicação: 2015
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/7860
• topic: Nitric oxide; Oxidative stress; Platelets; Bipolar disorder; Óxido nítrico; Estresse oxidativo; Plaquetas; Transtorno bipolar; Óxido nítrico; Estresse oxidativo; Plaquetas; Transtorno bipolar; Doenças cardiovasculares; CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA

Psychiatric disorders are public health problems, ocuppying five of ten major causes of incapacitation in the world. Bipolar disorder (BD) is a mood disorder, according to DMS-IV (Diagnostic and Statistic Manual of Mental Disease), which affects about 1% of world population. Bipolar I disorder (BDI) is the most frequent among the BDs and is characterized by the presence of manic or mixed episodes accompanied by depressive episodes. Similarly to other psychiatric disorders, such as depression, anxiety and schizophrenia, BD represents an important cardiovascular risk factor, and patients with this disorder have twice the cardiovascular mortality expected from general population. However, the exact mechanisms underlying this relationship remain unknown. Studies suggest the involvement of L-arginine-nitric oxide (NO) pathway on the pathogenesis of BD. NO is responsible for several physiological functions, including platelet function inhibition. L-arginine, its precursor, is transported into platelets by y+L carrier, and activates the enzyme NO synthase (NOS), which produces NO and L-citrulline. Once produced, NO activates the enzyme guanilyl cyclase (GC), increasing cyclic guanosine monophosphate (cGMP) levels. Additionally, L-arginine is not exclusively used by NOS, it can also be metabolized by arginase and produce L-ornithine and urea. NO bioavailability depends on both its synthesis and its degradation by oxidative stress and inflammation. The aim of this study was to investigate in detail L-arginine-NO-cGMP pathway in platelets of BDI patients, arginase expression and other markers that can affect NO bioavailability, such as oxidative stress and inflammation. Twenty eight patients with BD and ten healthy volunteers were included in this study. Our results showed decreased NOS activity in all groups of BDI patients (euthymic, depressive and manic episodes), when compared with controls. This occurred in the presence of normal substrate concentrations and unchanged expressions of eNOS and iNOS isoforms. Arginase II expression was not different between studied groups, indicating that L-arginine availability is not shifted to urea cycle in platelets. Decreased GMPc production was observed even in inalthered expression of GC. Activity and oxidative stress markers, evaluated through protein oxidation quantification and SOD and catalase activity, were not modified in platelets of BD patients while SOD activity was increased in all groups. Serum C-reactive protein (CRP) levels, an inflammatory marker, were higher in manic patients, compared with controls. The reduced production of NO observed in platelets of bipolar patients can be a link in this complex association between BD and cardiovascular disease.