Pharmacological Interventions on Asymmetric Dimethylarginine, a Clinical Marker of Vascular Disease

M.      Marin; S.      Manez

Abstract

The aim of this paper is to review the latest data on the pharmacological modulation of asymmetric dimethylarginine in human disease. When the terminal nitrogens of the guanidine portion of an arginine become methylated through the action of N-methyl transferases, two chemically close, but physiologically different amino acids are synthesized: symmetric and asymmetric dimethylarginine. The vascular origin of asymmetric dimethylarginine and its inhibitory activity on endothelial nitric oxide synthase give it an important role in certain diseases in which microcirculation is compromised: hypertension, atherosclerosis, inflammatory bowel disease, and diabetes. This review discusses the role that asymmetric dimethylarginine plays in the development of vascular disease, and, wherever possible, evaluates its use in clinical diagnosis. The fact that a number of chemically unrelated drugs, such as angiotensin II antagonists, selective beta- 1 adrenergic antagonists, plant phenolics, statins, and farnesoid X receptor agonists have all been found to reduce dimethylarginine levels in plasma or tissue allows for an integrated study. Although it is difficult to determine exactly why these various agents all have the same effect on arginine metabolism, an explanation of their mechanisms of action is needed. We have thus analyzed the mechanisms involved and reviewed potential trends in the therapeutic use of these drugs.

Keywords: Asymmetric dimethylarginine, cardiovascular diseases, nitric oxide, protein post translational modifications