Special Issue "ADMA and Nitrergic System"
Deadline for manuscript submissions: closed (30 December 2013)
Dr. Lorenza Speranza
Department of Medicine and Science of Aging, Applied Biology, “G. D’Annunzio” University, Chieti-Pescara, Italy
Fax: +39 0 8713554551
Interests: Oxidative stress; nitric oxide; nitric oxide synthase; natural compounds; asymmetric dimethylarginine; aging; brain natriuretic peptide; interleukin
Nitric oxide (NO) is one of the most important mediators synthesized from L-arginine by a family of NO synthases (NOS), involved in the regulation of vascular tone, neurotransmission in the central and peripheral nervous system, and regulation of mitochondrial respiration. The availability of NO in a given cell depends on many factors including expression and activity of several NOS (neuronal, inducible, and endothelial), abundance of NOS substrate, L-arginine, and its cofactor, tetrahydrobiopterin. NO production may also be regulated by endogenous NOS inhibitors, in particular asymmetric dimethylarginine (ADMA), synthesized during the methylation of protein arginine residues by protein arginine. ADMA is a competitive inhibitor of NOS, decrease NO availability and is eliminated by renal excretion or metabolized by dimethylarginine dimethylaminohydrolases (DDAH) to citruline and dimethylamine. Two other endogenous methylarginines are also synthesized by protein-arginine methyltransferases (PRMT): N-monomethyl-L-arginine (L-NMMA) and symmetric dimethylarginine (SDMA).
Plasma concentration of ADMA is increased in patients with hyperlipidemia, diabetes mellitus, arterial hypertension, hyperhomocysteinemia, heart and chronic renal failure. The increased concentration of ADMA is positively correlated with markers of atherosclerosis, such as carotid artery intima-media thickness and has a predictive value for acute cardiovascular events.
There is no doubt that ADMA regulate NOS activity under physiological and pathological conditions, is increased in many diseases in which NO deficiency, is metabolized by the endothelium and may represent an important index of endothelial dysfunction. The possibility to modulate ADMA by pharmacotherapy is a new and important approach of many acute and chronic disease and is still of great interest. Some medication such angiotensin converting enzyme inhibitors and angiotensin AT1 receptor antagonists, fibrates, metformin, antioxidant vitamins, aspirin, n-3 polyunsaturated fatty acids and flavonoids are drugs and substances which have shown to reduce ADMA levels in humans with the improvement of NO synthesis. Agents modifying ADMA concentrations should be considered in the treatment of many chronic diseases.
Dr. Graziano Riccioni
Dr. Lorenza Speranza
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- asymmetric dimethylarginine
- nitric oxide; nitric oxide synthase
- symmetric dimethylarginine
- dimethylarginine dimethylaminohydrolases
- protein-arginine methyltransferases
- reactive oxygen species