Effects of nutritional status on the L-arginine-nitric oxide pathway in platelets from hemodialysis patients.
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.
da Silva
Clarissa Demézio
CD
Departamento de Farmacologia e Psicobiologia, Universidade do Estado do Rio de Janeiro, Brazil.
Brunini
Tatiana M C
TM
Reis
Patrícia F
PF
Moss
Monique B
MB
Santos
Sérgio F F
SF
Roberts
Norman B
NB
Ellory
John C
JC
Mann
Giovanni E
GE
Mendes-Ribeiro
Antônio C
AC
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
D000596:Amino Acids; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP