The Endogenous Nitric Oxide Synthase Inhibitor ADMA and Cerebrovascular Disease

REVIEW ARTICLE


Fabian Muller¹, Rainer H Boger², Sudha Seshadri^3,4 and Renke Maas¹

Affiliations: ¹Institute of Experimental and Clinical Pharmacology and Toxicology, University Erlangen-Nuremberg, Erlangen, Germany; ²Institute of Experimental and Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; ³The National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, MA, USA and ⁴Department of Neurology, School of Medicine, Boston University, Boston, MA, USA

ABSTRACT

This review gives an overview of currently available data from clinical studies relating the endogenous nitric oxide (NO) synthase inhibitor asymmetrical dimethylarginine (ADMA) to cerebrovascular disease. In the majority of studies, ADMA plasma concentration correlates positively with the intima media thickness of the carotid artery. Moreover, elevation of plasma ADMA predicts prevalent cerebrovascular disease, progression of atherosclerosis, and adverse clinical outcome. Data from in vitro experiments and infusion studies in mice and men suggest that inhibition of NO synthesis by ADMA is a plausible pathomechanism behind these clinical findings. However, ADMA plasma concentrations associated with discernible differences in atherosclerotic burden in population‐based studies are substantially lower than ADMA concentrations required to elicit functional effects in vitro. A further investigation of the metabolism and distribution of ADMA in vivo may help to resolve these issues.

Keywords: Asymmetric dimethylarginine, ADMA, Carotid artery, Intima‐media thickness, Atherosclerosis, Nitric oxide synthase
Correspondence: R Maas, Institute of Experimental and Clinical Pharmacology and Toxicology, University Erlangen‐Nuremberg, Fahrstrasse 17, 91054 Erlangen, Germany. Tel: (49)‐9131‐85‐22754; Fax: (49)‐9131‐85‐22773; e‐mail: renke.maas@pharmakologie.uni‐erlangen.de