Nitric oxide (NO) is a molecule that mediates key physiological and pathophysiological mechanisms. The intracellular availability of L-arginine, the precursor for NO synthesis, is limited by plasma concentration, metabolism and L-arginine transport. The membrane transport of extracellular L-arginine seems to be a rate-limiting step for NO synthesis even when the intracellular levels of L-arginine are available in excess. A clear explanation for the phenomenon ´´Larginine paradox´´ has not yet been found. In mammalian cells, four transport systems for L-arginine have been described: y+, y+L, Bo,+ and bo,+. Chronic renal failure (CRF), chronic heart failure (CHF) and essential hypertension are characterised by endothelial dysfunction, elevated concentration of pro-inflammatory circulating cytokines and alteration in platelet function and coagulation factors. Due to these pathological alterations they comprise groups of patients at very high risk for atherothrombotic events. Accumulating evidence suggests that a disturbance of the L-arginine-NO pathway is involved in the pathophysiology of CRF, CHF and hypertension, perhaps reflecting a response to the hormonal imbalance and increased production of inflammatory mediators common to these diseases. The current review provides an overview of L-arginine transport and NO production in endothelium and blood cells in patients with cardiovascular and renal diseases.
Keywords: chronic renal failure, chronic heart failure, essential hypertension, cytokines, inflammation, nitric oxide, larginine, blood cells, endothelium, uraemia
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