GC-MS assay for hepatic DDAH
activity in diabetic and non-diabetic rats by measuring dimethylamine (DMA) formed from asymmetric dimethylarginine (ADMA): evaluation of the importance of S-nitrosothiols as inhibitors of DDAH
activity in vitro and in vivo in humans.
Homocysteine induced accumulation of asymmetric dimethylarginine: role of DDAH
and effect of antioxidants.
Both isoforms of DDAH have been shown to be sensitive to oxidative stress (26), and ADMA concentrations tend to rise under conditions of oxidative stress (27).
This study was the first to investigate a complete (lipid and water soluble) extract of cigarette smoke; previous studies reporting divergent results on ADMA and DDAH expression used only the water-soluble fraction of cigarette smoke (30) or nicotine at cytotoxic levels (31) or investigated ADMA concentrations in regenerated endothelial cells from carotid arteries obtained 6 weeks after endothelial removal in rabbits chronically exposed to nicotine (32).
Upregulation of DDAH expression should not raise too much enthusiasm in smokers, though.
Homocysteine also cause the inhibition of DDAH
, which is the enzyme responsible for the catabolism of ADMA, leading further increase in plasma ADMA level (27).
These conditions are associated with vascular oxidative stress, which is known to impair DDAH activity (8).
The results of the present study suggest that it might be worthwhile to readdress this issue, especially because new, specific drugs that increase DDAH expression and lower ADMA, like the farnesoid X receptor agonist GW 4064, are still in the early stage of development (18).
2) mmHg, (39), and mice with low ADMA as a consequence of DDAH overexpression exhibit a modest decrease in blood pressure (40).
6] Nonstandard abbreviations: ADMA, asymmetrical dimethylarginine; ESRD, end-stage renal disease; CAD, coronary artery disease; LURK, Ludwigshafen Risk and Cardiovascular Health study; CRP, C-reactive protein; NSTEMI, non-ST-elevation myocardial infarction; MI, myocardial infarction, STEMI, ST-elevation MI; GFR, glomerular filtration rate; HDL-C, HDL cholesterol; LDL-C, LDL cholesterol; BMI, body mass index; HR, hazard ratio; DDAH, dimethyl-arginine dimethylaminohydrolase.