title: Asymmetric dimethylarginine, endothelial dysfunction and renal disease.
abstract: l-Arginine (Arg) is oxidized to l-citrulline and nitric oxide (NO) by the action of endothelial nitric oxide synthase (NOS). In contrast, protein-incorporated Arg residues can be methylated with subsequent proteolysis giving rise to methylarginine compounds, such as asymmetric dimethylarginine (ADMA) that competes with Arg for binding to NOS. Most ADMA is degraded by dimethylarginine dimethyaminohydrolase (DDAH), distributed widely throughout the body and regulates ADMA levels and, therefore, NO synthesis. In recent years, several studies have suggested that increased ADMA levels are a marker of atherosclerotic change, and can be used to assess cardiovascular risk, consistent with ADMA being predominantly absorbed by endothelial cells. NO is an important messenger molecule involved in numerous biological processes, and its activity is essential to understand both pathogenic and therapeutic mechanisms in kidney disease and renal transplantation. NO production is reduced in renal patients because of their elevated ADMA levels with associated reduced DDAH activity. These factors contribute to endothelial dysfunction, oxidative stress and the progression of renal damage, but there are treatments that may effectively reduce ADMA levels in patients with kidney disease. Available data on ADMA levels in controls and renal patients, both in adults and children, also are summarized in this review.
authors.affiliation: Division of Metabolism, Cruces University Hospital, Barakaldo, Basque Country 48903, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Aldámiz-Echevarría
authors.affiliation: Division of Metabolism, Cruces University Hospital, Barakaldo, Basque Country 48903, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Andrade
mesh_terms: D000328:Adult; D000581:Amidohydrolases / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000473:pathology*; D002648:Child; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D007674:Kidney Diseases / Q000473:pathology*; D016030:Kidney Transplantation; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000737:chemistry; D018384:Oxidative Stress; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D000581:Amidohydrolases; C059999:dimethylargininase
keywords: arginine (Arg); asymmetric dimethylarginine (ADMA); children; dimethylarginine dimethylaminohydrolase (DDAH); endothelial dysfunction; kidney; methylarginines; nitric oxide; oxidative stress; renal failure