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 nitric oxide (NO) may be elevated in both pathological syndromes, enhanced production of NO fails to overcome endothelial dysfunction. Plasma concentrations of L-arginine, a cationic amino acid precursor for NO synthesis, are reduced whilst levels of the endogenous L-arginine analogues, asymmetric and symmetric dimethyl arginine and N(G)-monomethyl-L-arginine, seem to be elevated. 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, peripheral blood mononuclear cells and platelets from both patients with either chronic renal or heart failure. A possible explanation why NO serves as a failing counter-regulatory mechanism in both these pathologies is that availability of L-arginine for NO production is reduced despite the observed increase in membrane transport. This review examines the mechanisms underlying alterations in NO production in chronic renal and heart failure, and the possible role of L-arginine transport in vascular and platelet dysfunction observed in both syndromes.
University Laboratory of Physiology, South Parks Road, OX1 3PT, Oxford, UK. cribeiro@physiol.ox.ac.uk
A C
AC
Mendes Ribeiro
T M
TM
Brunini
J C
JC
Ellory
G E
GE
Mann
D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001692:Biological Transport; D001792:Blood Platelets / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D023421:Models, Animal; D009569:Nitric Oxide / Q000378:metabolism*; D015398:Signal Transduction; D014511:Uremia / Q000378:metabolism
D016207:Cytokines; D009569:Nitric Oxide; D001120:Arginine