The Role of Asymmetric Dimethylarginine and Arginine in the Failing Heart and its Vasculature

Marlieke Visser; Walter J. Paulus; Mechteld A.R. Vermeulen; Milan C. Richir; Mariska Davids; Willem Wisselink; Bas A.J.M. de Mol; Paul A.M. van Leeuwen

Disclosures

Eur J Heart Fail. 2010;12(12):1274-1281. 

In This Article

Summary and Conclusion

By inhibiting NOS, ADMA affects the correct functioning of the heart; studies have shown that ADMA is involved in vasoconstriction, cardiac remodelling, fibrosis, disturbance of angiogenesis and cardiac performance, myocardial ischaemia, and even mortality. These results show that ADMA is not only a risk factor for cardiovascular disease, but also an indicator of outcome in patients with cardiac dysfunction. The elevated ADMA levels shown in cardiac disorders are thought to be the result of diminished activity and/or expression of its metabolizing enzyme DDAH. Upregulation of DDAH has been shown to reduce ADMA with a concomitant increase in NO production resulting in beneficial effects for the heart and its vasculature. As ADMA competes with arginine for NOS binding, the net amount of NO might not only depend on ADMA levels but also on arginine concentrations, which can be reflected by the arginine/ADMA ratio.

Arginine levels can be insufficient under catabolic conditions in which arginase catalyses arginine. Interestingly, increased extracellular arginine can be taken up by endothelial cells and can contribute to NO synthesis. Therefore, arginine supplementation, especially by infusion, seems beneficial under conditions of cardiac dysfunction without inflammation. The impact of the arginine precursors citrulline and glutamine is less apparent. More research is needed to investigate the ability of nutritional therapies to increase the arginine/ADMA ratio directly or indirectly via its degrading enzymes arginase and DDAH, respectively, which might enhance NO availability with a concomitant improvement in cardiac function.

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