Abnormalities in L-arginine transport and nitric oxide biosynthesis in chronic renal and heart failure

Patients with chronic renal and heart failure present with hypertension and widespread vasoconstriction, respectively. Although systemic release of ni tric oxide (NO) may be elevated in both pathological syndromes, enhanced pr oduction of NO fails to overcome endothelial dysfunction. Plasma concentrat ions of L-arginine, a cationic amino acid precursor for NO synthesis, are r educed whilst levels of the endogenous L-arginine analogues, asymmetric and symmetric dimethyl arginine and N-G-monomethyl-L-arginine, seem to be elev ated. We have reported that transport of L-arginine via the cationic amino acid transporters y(+)/CAT and/or y(+)L are up-regulated in erythrocytes, p eripheral blood mononuclear cells and platelets from both patients with eit her chronic renal or heart failure. A possible explanation why NO serves as a failing counter-regulatory mechanism in both these pathologies is that a vailability of L-arginine for NO production is reduced despite the observed increase in membrane transport. This review examines the mechanisms underl ying alterations in NO production in chronic renal and heart failure, and t he possible role of L-arginine transport in vascular and platelet dysfuncti on observed in both syndromes. (C) 2001 Elsevier Science BN. All rights res erved.