Division of Nephrology, Department of Internal Medicine, Hannover Medical School, Hannover, Germany (D. Fliser).
Asymmetric dimethylarginine (ADMA): the silent transition from an ‘uraemic toxin’ to a global cardiovascular risk molecule
Version of Record online: 24 JAN 2005
European Journal of Clinical Investigation
Volume 35, Issue 2, pages 71–79, February 2005
How to Cite
Fliser, D. (2005), Asymmetric dimethylarginine (ADMA): the silent transition from an ‘uraemic toxin’ to a global cardiovascular risk molecule. European Journal of Clinical Investigation, 35: 71–79. doi: 10.1111/j.1365-2362.2005.01457.x
- Issue online: 24 JAN 2005
- Version of Record online: 24 JAN 2005
- Received 23 November 2004; accepted 1 December 2004
- Asymmetric dimethylarginine;
- cardiovascular risk;
- dimethylarginine dimethylaminohydrolase;
- nitric oxide;
- renal dysfunction
Endothelial dysfunction as a result of reduced bioavailability of nitric oxide (NO) plays a central role in the process of atherosclerotic vascular disease. In endothelial cells NO is synthesized from the amino acid l-arginine by the action of the NO synthase (NOS), which can be blocked by endogenous inhibitors such as asymmetric dimethylarginine (ADMA). Acute systemic administration of ADMA to healthy subjects significantly reduces NO generation, and causes an increase in systemic vascular resistance and blood pressure. Increased plasma ADMA levels as a result of reduced renal excretion have been associated with atherosclerotic complications in patients with terminal renal failure. However, a significant relationship between ADMA and traditional cardiovascular risk factors such as advanced age, high blood pressure and serum LDL-cholesterol, has been documented even in individuals without manifest renal dysfunction. As a consequence, the metabolism of ADMA by the enzyme dimethylarginine dimethylaminohydrolase (DDAH) has come into the focus of cardiovascular research. It has been proposed that dysregulation of DDAH with consecutive increase in plasma ADMA concentration and chronic NOS inhibition is a common pathophysiological pathway in numerous clinical conditions. Thus, ADMA has emerged as a potential mediator of atherosclerotic complications in patients with coronary heart disease, peripheral vascular disease, stroke, etc., being the culprit and not only an innocent biochemical marker of the atherosclerotic disease process.