Effects of nutritional status on the L-arginine-nitric oxide pathway in platelets from hemodialysis patients

Effects of nutritional status on the L-arginine-nitric oxide pathway in platelets from hemodialysis patients.BackgroundMalnutrition 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.MethodsPlatelet aggregation was correlated with plasma amino acid profiles, L-arginine transport, and nitric oxide synthase (NOS) activity determined by conversion of L-[3H]-arginine to L-[3H]-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).ResultsTransport of L-arginine (pmol/109cells/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/108cells) 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.ConclusionOur 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.