ADMA Asymmetric

Asymmetric dimethylarginine (ADMA). Asymmetric dimethylarginine (ADMA) potently impairs the vascular endothelial function by inhibiting the production of nitric oxide (NO) through the antagonism with arginine, a substrate of NO. 

Homocysteine decreases the bioavailability of nitrous oxide (NO) via a mechanism involving glutathione peroxidase (37). Tawakol et al. (38) reported that hyperhomocysteinemia is associated with impaired endothelium-dependent vasodilation in humans. Homocysteine impairs the NO synthase pathway both in cell culture (39) and in monkeys with hyperhomocysteinemia, by increasing the levels of asymmetric dimethylarginine (ADMA), an endogenous NO synthase inhibitor (40). Elevation of ADMA may mediate endothelial dysfunction during experimental hyperhomocysteinemia in humans (41). However, Jonasson et al. (42) did not find increased ADMA levels in patients with coronary heart disease and hyperhomocysteinemia, nor did vitamin supplementation have any effect on ADMA levels in spite of substantial plasma tHcy reduction,... 

I CAM-1, VCAM-1, and endothelin-1 concentrations were significantly greater in men with ED and no cardiovascular disease symptoms compared to men without ED (24). Asymmetric demethyl arginine (ADMA) is an endogenous competitive nitric oxide (NO) synthase inhibitor and is an independent risk marker for cardiovascular disease impairing the L-arginine-NO pathway. Recent studies have found elevated levels of ADMA in men with ED and CAD (25 — 27). 

Maas R, Wenske S, Zabel M, et al. Elevation of asymmetrical dimethylarginine (ADMA) and coronary artery disease in men with erectile dysfunction. Eur Urol 2005 48 1004-1012. 

Let s start with this one because arginine is the raw material, the substrate, from which NO is made in the endothelium. To get the job done, you must have an adequate amount of eNOS, the enzyme that acts as a catalyst in the production process, and enough of the amino acid arginine. But the process can be blocked by high levels of asymmetric dimethylarginine (ADMA), a known inhibitor of NO synthesis. 

DDAH itself may also have potential as a therapeutic protein in disease states marked by excess N dimethyl-L-arginine. For example, overexpression of DDAH has beneficial effects in transgenic mouse models of graft coronary artery disease and can enhance sensitivity to insulin. DDAH may also have beneficial effects in treating chronic kidney disease, as overexpressed DDAH appears to slow progression of renal dysfunction in rat models. " Elevated asymmetric dimethylarginine (ADMA) levels have also been identified in the development of chronic lung diseases, specifically pulmonary fibrosis. However, the causal relationship between ADMA and these conditions has yet to be explored in detail. ... 

Fig. 9. Plasma asymmetric dimethyl arginine (ADMA), a compound detectable in human plasma and an endogenous inhibitor of endothelial nitric oxide synthase (eNOS), increases after a fat meal in diabetic patients. It is associated with an increase in plasma triglycerides and impaired flow-mediated (FM) vasodilation [data from Fard etal. (92), reproduced with permission]. The increase in plasma ADMA in response to the high-fat meal was significantly and inversely related to a decrease in the percentage of vasodilation (r = -0.37, P= 0.007, n = 10).

Stefanadis, C., and Channon, K.M., 2009b. Association of plasma asymmetrical dimethylarginine (ADMA) with elevated vascular superoxide production and endothelial nitric oxide synthase uncoupling implications for endothelial function in human atherosclerosis. European Heart Journal. 30 1142 1150. 

Homocysteine metabolism is involved both in the synthesis and degradation of asymmetric dimethylarginine (ADMA), a potent endogenous NO-synthase inhibitor, which is thought to be an independent predictor of cardiovascular mortality in end-stage renal disease. 

Asymmetric dimethylarginine (ADMA), a potent endogenous nitric oxide (NO) synthase inhibitor. 

In patients with atheromas levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NOS, are increased and correlated with endothelial dysfunction (reviewed in ref. 57). Dimethylarginines... 

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