Table 1: Modulation of the L-Arginine-NO Pathway in Chronic Heart Failure

Reported Change Summary of Findings Reference
NOS activity/ NOS expression/ nitrite+nitrate production /cGMP Increased ↑ plasma nitrate levels Chowdhary, et al. 2002
Increased ↑ vasoconstrictor effect of L-NMMA Dover et al. 2006
Decreased L-arginine administration ↓ vascular resistance associated with ↑ nitrate/nitrite production Katz et al. 1999
Increased ↑ NO plasma concentration Kaye et al. 1998
Increased ↑ iNOS expression in skeletal muscle Stein et al. 1998
Increased ↑ iNOS expression and iNOS protein content in skeletal muscle inversely correlated with changes in COX-activity and the exercise Gielen et al. 2005
Increased ↑ endomyocardial eNOS or iNOS gene expression augments LV stroke volume and LV stroke work Heymes et al. 1999
Decreased ↓ activity of the L-arginine-NO metabolic pathway Katz et al. 1999
Increased iNOS, but not eNOS expression in ventricular myocardium Drexler et al. 1999
Increased ↑ plasma nitrite level Yu et al. 2001
Increased ↑ iNOS expression in the myocardium and ↑ serum concentration of nitrate/nitrite Orús et al. 2000
Increased ↑ NO plasmatic concentation which showed positive correlation with TNF-α plasmatic levels Elahi et al. 2007
Increased/decreased ↑ iNOS activity and expression, but ↓ eNOS activity and expression in failing hearts Ferreiro et al. 2004
Unaltered There was no difference in exhaled NO between controls and heart failure patients, nor after exercise Seshadri et al. 2003
Endothelial function Decreased responses vasodilatador endothelium-dependent induce by acetylcholine in braquial artery Morgan et al. 2004
Decreased ↓ forearm blood flow Ishibashi et al. 2000
Decreased ↓ vasodilatation endothelium-dependent in forearm Heitzer et al. 2005
Increased Vitamin C improves endothelium-dependent forearm vasodilatation Hirooka et al. 2003
Decreased ↓ endothelium-dependent vasodilatation in response to aceylcholine in internal radial artery was improved by oral L-arginine supplementation and exercise training. Hambrecht et al. 2000
Decreased ↓ forearm blood flow Bank et al. 2000
Decreased ↓ forearm blood flow in response to acetylcholine. Sugamori et al. 2002
L-arginine transport Increased ↑ L-arginine transport via system y+ in erythrocytes from heart failure patients associated with ↓ plasmatic levels of L-arginine and ↑­ plasmatic levels of L-NMMA Hanssen et al. 1998

L-NMMA, NG-monomethyl L-arginine; NO, nitric oxide; NOS, nitric oxide synthase; iNOS, inducible nitric oxide synthase; eNOS, endothelial nitric oxide synthase; PBMCs, peripheral blood mononuclear cells; COX, cytochrome e oxidase.