title: Low plasma levels of L-arginine, impaired intraplatelet nitric oxide and platelet hyperaggregability: implications for cardiovascular disease in depressive patients.
abstract: 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±4years) and 19 control subjects (CS, 34±3years) were included. L-[(3)H]-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departamento de Farmacologia e Psicobiologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Vivian Liane Mattos
authors.initials: VL
authors.lastname: Pinto
authors.forename: Paula Fontoura Coelho
authors.initials: PF
authors.lastname: de Souza
authors.forename: Tatiana Marlowe Cunha
authors.initials: TM
authors.lastname: Brunini
authors.forename: Monique Bezerra
authors.initials: MB
authors.lastname: Oliveira
authors.forename: Monique Bandeira
authors.initials: MB
authors.lastname: Moss
authors.forename: Mariana Alves de Sá
authors.initials: MA
authors.lastname: Siqueira
authors.forename: Marcos Rochedo
authors.initials: MR
authors.lastname: Ferraz
authors.forename: Antônio Cláudio
authors.initials: AC
authors.lastname: Mendes-Ribeiro
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000097:blood; D001120:Arginine / Q000097:blood* / Q000378:metabolism; D001792:Blood Platelets / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D006152:Cyclic GMP / Q000378:metabolism; D003865:Major Depressive Disorder / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010974:Platelet Aggregation / Q000502:physiology*; D012307:Risk Factors
chemical_list: D000596:Amino Acids; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D006152:Cyclic GMP