Proceedings of The Physiological Society

University of Oxford (2011) Proc Physiol Soc 23, PC305

Poster Communications

L-Arginine-nitric oxide pathway and possible implications for cardiovascular disease in depressive patients

V. Pinto1, P. C. Fontoura1, M. B. Oliveira1, C. R. da Silva1, A. Mendes-Ribeiro1,2, T. M. Brunini1

1. Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. 2. Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.


Introduction: Major depressive disorder (MDD) represents an important cardiovascular risk factor, and patients with this disorder have twice the cardiovascular mortality expected from the general population (1, 2). However, the exact mechanisms underlying this relationship remain unknown. Studies suggest the involvement of the L-arginine-nitric oxide (NO) pathway in the pathogenesis of MDD (3). NO is responsible for several physiological functions, including platelet function inhibition, neurotransmission and vasodilatation (4). The aim of study was to investigate the role L-arginine-nitric oxide pathway in platelets from patients with MDD. Methods: Ten patients with MDD meeting DSM IV criteria and without any medication (4 males and 6 females, mean age: 38±11years), were paired with ten normal control subjects (CS). The Pedro Ernesto Hospital Ethical Committee approved this study (1436- CEP/HUPE), and informed consent was obtained from each participant. Extracellular L-arginine transport into platelets was measured by kinetic methods, using crescent concentrations of [3H] L-arginine. NOS activity was evaluated by the conversion of [H3]L-arginine into [3H]L-citrulline, and cGMP content was determined in washed platelets at baseline using a commercial ELISA method. L-arginine concentration was measured by high-performance liquid chromatography (HPLC) method. The Mann-Whitney U test or unpaired test was used to analyze the differences between MD and (CS), in accordance with the Kolmogorov-Smirnov test. Values were expressed as means ±SEM. A p value of less than .05 was considered significant. Results: L-arginine transport via the y+L system (pmol/109 cells/min) into platelets was decreased in MDD (CS: 46±9, MDD: 20±2, p<.05). Basal NOS activity (pmol/108 cells) was diminished in platelets from MDD (0,16±0,01) compared to CS (0,09±0,01), p<.05. cGMP content (pmol/108 cells) was reduced in MDD (0.04 ± 0.001) compared with CS (0.11 ± 0.02), p<.05. L-arginine concentration (µM) was also decreased in plasma from MDD patients (104 ± 4) in relation to CS (130 ± 8), p<.05. Discussion: We have verified an impairment of L-arginine transport into platelets with subsequent reduced NO production cGMP content. A diminished concentration of plasma levels L-arginine could reduce transmembrane transport and consequently intracellular substrate for NOS in platelets with MDD. It is possible that an impairment of the L-arginine-NO-GMPc pathway might be an early marker of future platelet activation and thrombotic events in MDD patients.

Where applicable, experiments conform with Society ethical requirements