Copyright © 2006, European Society of Cardiology
Platelet nitric oxide synthesis in uremia and malnutrition: A role for L-arginine supplementation in vascular protection?
aDepartamento de Farmacologia e Psicobiologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-030, Brazil
bDisciplina de Farmacologia, Departamento de Ciências Fisiológicas, Universidade Federal do Estado do Rio de Janeiro, Brazil
cUniversity Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK
dCardiovascular Division, School of Biomedical and Health Sciences, King's College London, Guy's Campus, London SE1 1UL, UK
* Corresponding author. Cardiovascular Division, King's College New Hunt's House (Rm 2.34B), Guy's Campus, London SE1 1UL, UK. Tel.: +44 20 7848 6209; fax: +44 20 7848 6220. Email address: giovanni.mann{at}kcl.ac.uk
L-arginine is the physiological precursor for nitric oxide (NO) synthesis, and availability and transport of L-arginine modulate the rates of NO biosynthesis in circulating blood cells and the vasculature. NO is involved in many vascular functions such as vasodilation and inhibition of platelet aggregation and adhesion. We have established that reduced plasma L-arginine and NO production and increased tumour necrosis factor-alpha (TNF-
), fibrinogen, and C-reactive protein levels in malnourished uremic patients are associated with increased aggregability of platelets. Our findings may explain the increased cardiovascular mortality in patients with deficient nutritional status, leading to inflammation, oxidative stress, impaired L-arginine–NO signalling, and platelet activation. The aim of this review is to evaluate whether disturbances in the L-arginine–NO signalling pathway in chronic renal failure and atherosclerosis are affected by malnutrition and inflammation. We have included a brief overview of membrane transporters mediating influx of L-arginine and other cationic amino acids, as these transporters are involved in the potential benefits of L-arginine supplementation and platelet function in malnourished uremic patients.
KEYWORDS Platelets; Uremia; Chronic renal failure; Malnutrition; L-arginine–nitric oxide signalling pathway; L-arginine; Nitric oxide; TNF-; C-reactive protein; Fibrinogen; L-arginine supplementation
Time for primary review 25 days
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