Limits...
Asymmetric dimethylarginine, endothelial dysfunction and renal disease.

Aldámiz-Echevarría L, Andrade F - Int J Mol Sci (2012)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Metabolism, Cruces University Hospital, Barakaldo, Basque Country 48903, Spain; E-Mail: fernando.andradelodeiro@osakidetza.net.

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.

Show MeSH

Related in: MedlinePlus

Nitric oxide (NO) synthesis in vascular endothelium and its diffusion to smooth-muscle cells where soluble guanylyl cyclise (sGC) is stimulated resulting in enhanced synthesis of cyclic guanosine monophosphate (GMP).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC3472745&req=5

f1-ijms-13-11288: Nitric oxide (NO) synthesis in vascular endothelium and its diffusion to smooth-muscle cells where soluble guanylyl cyclise (sGC) is stimulated resulting in enhanced synthesis of cyclic guanosine monophosphate (GMP).

Mentions: The vascular endothelium has many functions and, accordingly, endothelial dysfunction is responsible for numerous health problems including atherosclerosis, high blood pressure, sepsis, thrombosis, vasculitis, and bleeding, among others. One of the most important functions of the endothelium is to secrete nitric oxide (NO), a relatively unstable diatomic free radical, which can be synthesized by a broad range of organisms. This molecule has a role as a messenger in many biological processes in humans including involvement in the regulation of neurone communication, antimicrobial activity, ventilation, hormone secretion, inflammation and immune responses well as vascular tone [3]. Indeed, it is a potent vasodilator and levels are often reduced when endothelial function is impaired, making it a vascular risk factor and, in particular, together with dyslipidaemia, a risk factor for coronary disease. Nitric oxide was first described as an endothelium-derived vascular relaxant factor, but its role in vasodilation depends on an increase in the levels of cyclic guanosine monophosphate (cGMP) in smooth muscle cells (Figure 1). In this case, NO is synthesized from arginine by the enzyme nitric oxide synthase (NOS), which has been identified in neurons, endothelial cells, macrophages and hepatocytes in various different isoforms: inducible (iNOS) and constitutive (cNOS), which contains neuronal (nNOS), and endothelial (eNOS).


Asymmetric dimethylarginine, endothelial dysfunction and renal disease.

Aldámiz-Echevarría L, Andrade F - Int J Mol Sci (2012)

Nitric oxide (NO) synthesis in vascular endothelium and its diffusion to smooth-muscle cells where soluble guanylyl cyclise (sGC) is stimulated resulting in enhanced synthesis of cyclic guanosine monophosphate (GMP).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472745&req=5

f1-ijms-13-11288: Nitric oxide (NO) synthesis in vascular endothelium and its diffusion to smooth-muscle cells where soluble guanylyl cyclise (sGC) is stimulated resulting in enhanced synthesis of cyclic guanosine monophosphate (GMP).
Mentions: The vascular endothelium has many functions and, accordingly, endothelial dysfunction is responsible for numerous health problems including atherosclerosis, high blood pressure, sepsis, thrombosis, vasculitis, and bleeding, among others. One of the most important functions of the endothelium is to secrete nitric oxide (NO), a relatively unstable diatomic free radical, which can be synthesized by a broad range of organisms. This molecule has a role as a messenger in many biological processes in humans including involvement in the regulation of neurone communication, antimicrobial activity, ventilation, hormone secretion, inflammation and immune responses well as vascular tone [3]. Indeed, it is a potent vasodilator and levels are often reduced when endothelial function is impaired, making it a vascular risk factor and, in particular, together with dyslipidaemia, a risk factor for coronary disease. Nitric oxide was first described as an endothelium-derived vascular relaxant factor, but its role in vasodilation depends on an increase in the levels of cyclic guanosine monophosphate (cGMP) in smooth muscle cells (Figure 1). In this case, NO is synthesized from arginine by the enzyme nitric oxide synthase (NOS), which has been identified in neurons, endothelial cells, macrophages and hepatocytes in various different isoforms: inducible (iNOS) and constitutive (cNOS), which contains neuronal (nNOS), and endothelial (eNOS).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Metabolism, Cruces University Hospital, Barakaldo, Basque Country 48903, Spain; E-Mail: fernando.andradelodeiro@osakidetza.net.

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.

Show MeSH
Related in: MedlinePlus