title: Effects of nutritional status on the L-arginine-nitric oxide pathway in platelets from hemodialysis patients.
abstract: BACKGROUND
  Malnutrition is a common feature in chronic renal failure and adversely affects patient morbidity and mortality. We here investigate the effects of nutritional status on the L-arginine-nitric oxide signaling pathway and platelet function in chronic renal failure patients on regular hemodialysis.
  
  
  METHODS
  Platelet aggregation was correlated with plasma amino acid profiles, L-arginine transport, and nitric oxide synthase (NOS) activity determined by conversion of L-[(3)H]-arginine to L-[(3)H]-citrulline and accumulation of intracellular cyclic guanosine monophospate (cGMP) in platelets from malnourished and well-nourished chronic renal failure patients on regular hemodialysis (N = 78).
  
  
  RESULTS
  Transport of L-arginine (pmol/10(9)cells/min) via y(+) L system was increased in well-nourished (104 +/- 15) compared to controls (57 +/- 11) or malnourished chronic renal failure patients (55 +/- 13). Basal NOS activity (pmol/10(8)cells) was enhanced in well-nourished chronic renal failure patients (0.51 +/- 0.01) compared to controls (0.18 +/- 0.01) or malnourished chronic renal failure patients (0.08 +/- 0.03). In addition, basal cGMP levels are elevated in platelets from well-nourished chronic renal failure compared to malnourished uremic patients. Platelet aggregation induced by collagen is impaired in well-nourished chronic renal failure patients compared to malnourished patients and controls. Plasma L-arginine levels are reduced in chronic renal failure patients and even lower in malnourished patients.
  
  
  CONCLUSIONS
  Our findings provide the first evidence that L-arginine transport via the high affinity system y(+) L and nitric oxide synthesis are only stimulated in platelets from well-nourished chronic renal failure patients, leading to impaired platelet aggregation. The absence of this adaptive response in the l-arginine-nitric oxide pathway in platelets from malnourished chronic renal failure patients may account for the enhanced occurrence of thrombotic events in these patients.
authors.affiliation: Departamento de Farmacologia e Psicobiologia, Universidade do Estado do Rio de Janeiro, Brazil.
authors.forename: Clarissa Demézio
authors.initials: CD
authors.lastname: da Silva
authors.forename: Tatiana M C
authors.initials: TM
authors.lastname: Brunini
authors.forename: Patrícia F
authors.initials: PF
authors.lastname: Reis
authors.forename: Monique B
authors.initials: MB
authors.lastname: Moss
authors.forename: Sérgio F F
authors.initials: SF
authors.lastname: Santos
authors.forename: Norman B
authors.initials: NB
authors.lastname: Roberts
authors.forename: John C
authors.initials: JC
authors.lastname: Ellory
authors.forename: Giovanni E
authors.initials: GE
authors.lastname: Mann
authors.forename: Antônio C
authors.initials: AC
authors.lastname: Mendes-Ribeiro
mesh_terms: D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000097:blood; D001120:Arginine / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism* / Q000628:therapy; D008297:Male; D044342:Malnutrition / Q000178:diet therapy / Q000378:metabolism*; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009752:Nutritional Status; D010974:Platelet Aggregation; D006435:Renal Dialysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014511:Uremia / Q000178:diet therapy / Q000378:metabolism / Q000628:therapy
chemical_list: D000596:Amino Acids; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP