Low plasma levels of L-arginine, impaired intraplatelet nitric oxide and platelet hyperaggregability: Implications for cardiovascular disease in depressive patients

Background: Major depression (MD) is an independent cardiovascular risk factor, but the exact mechanisms are not clear. In this study we have investigated the intraplatelet L-arginine-nitric oxide (NO) pathway and platelet function in depressive patients. Methods: Nineteen unmedicated patients with MD (34 +/- 4 years) and 19 control subjects (CS, 34 +/- 3 years) were included. L-[H-3]-arginine influx, NO synthase (NOS) activity and intracellular cGMP levels were evaluated in platelets, as well as the expression of eNOS, iNOS, arginase and soluble guanylate cyclase (sGC), platelet aggregation and the systemic amino acid profile in MD patients and CS. Results: L-arginine influx (pmol/10(9)cells/min) in platelets was reduced from 46.2 +/- 9.5 to 20.02 +/- 2.12 in depression. NOS activity (pmol/10(8) cells) was diminished in MD patients (0.09 +/- 0.01) compared to CS (0.17 +/- 0.01). Intracellular cGMP levels were also impaired in MD patients associated with hyperaggregability. Moreover, the concentration of plasma L-arginine was reduced by 20% in MD patients. The expression of eNOS, iNOS, arginase II and sGC in platelet lysates was not affected by MD. Limitations: Small number of patients in the study. Conclusions: This study has demonstrated an impairment of L-arginine-NO signaling in platelets from MD patients, suggesting a role in platelet activation and cardiovascular events. (C) 2012 Elsevier B.V. All rights reserved.