Proceedings of The Physiological Society

University College Dublin (2009) Proc Physiol Soc 15, PC93B

Poster Communications

Platelet L-Arginine-Nitric Oxide Pathway in Bipolar Disorder

P. F. de Souza1, V. Pinto1, C. Elie2, M. Moss1, C. Matsuura1, O. da Silva1, T. Brunini1, M. Antônio Cláudio1

1. Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. 2. Instituto de Psiquiatris da Universidade do Rio de Janeiro, Rio de Janeiro, Brazil.

The bipolar disorder (BD) is a humor disorder, according to DMS-IV (Diagnostic and Statistic Manual of Mental Disease). This disorder affects approximately 1.5% of the population and it is characterized by the presence of mania and depression episodes. Similarly to other psychiatric disorders, such as depression, anxiety and schizophrenia, the BD is an important cardiovascular risk factor. However, the exact mechanisms underlying this relationship remain unknown. Recent studies suggest the involvement of L-arginine-nitric oxide pathway on the pathophysiology of BD. Nitric oxide (NO) is a lipophylic gas which is produced by different blood cells. L-arginine, it’s precursor, is transported to platelets by y+L carrier, and activates the enzyme NO synthase (NOS), which produces NO and L-citrulline. NO has many physiological functions, including: vasodilatation, neurotransmission and platelet aggregation inhibition. Despite intracellular concentration of L-arginine is above the Km of NOS, the extracellular transport of L-arginine is necessary for NO production. The aim of this study was to investigate L-arginine transport and NOS activity in platelet of bipolar patients. Nine patients with BD and nine healthy volunteers were included in this study. Extracellular L-arginine transport into platelet was measured by kinetic methods, using crescent concentrations of [3H] L-arginine; and NOS activity was evaluated by the conversion of [3H]L-arginine on [3H]L-citrulline. Data were presented by mean and standard error. The student t test was used for statistical analysis and statistic difference was considered when p<0.05. Total L-arginine transport (pmol L-arginine/108 cells/min) was similar in bipolar patients (Vmax total=95±31) and healthy controls (Vmax total=86±19). L-arginine transport via system y+L did not differ between bipolar patients (Vmax y+L=83±59), compared with healthy controls (Vmax y+L=43±10). NOS activity (pmol L-citrulline/109 cells) was reduced on bipolar patients (0.059±0.018) compared with controls (1.138±0.027) (p=0.04292). These results suggest that NO production by NOS is reduced in bipolar patients. This lower production of NO can be contributing for the higher cardiovascular risk factor seen in patients with BD. Our next step is to determine platelet function, to see if platelet aggregation is increased in these patients. This would increase the incidence of thrombotic events in bipolar patients.

Where applicable, experiments conform with Society ethical requirements