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Fenofibrate increases the l-arginine:ADMA ratio by increase of l-arginine concentration but has no effect on ADMA concentration

      Abstract

      Asymmetric dimethylarginine (ADMA), a guanidino-substituted analogue of l-arginine, is a potent endogenous competitive inhibitor of the endothelial nitric oxide synthase and therefore a potentially atherogenic amino acid. Hyperlipidemia and hyperhomocysteinemia have both been reported to be associated with elevated ADMA concentrations. Therefore, we investigated the influence of micronized fenofibrate (200 mg/day, 6 week treatment) on the l-arginine:ADMA ratio in 25 hypertriglyceridemic men. ADMA was neither associated to serum triglycerides, serum cholesterol, LDL-cholesterol or HDL-cholesterol or plasma total homocysteine at baseline. Treatment with fenofibrate did not alter plasma ADMA level, in contrast to serum triglycerides which were significantly lowered and plasma total homocysteine which was significantly increased. In addition, serum l-arginine levels significantly increased, leading to a higher l-arginine:ADMA ratio after treatment. The null effect of fenofibrate on plasma ADMA levels is in line with reported effects of other lipid-lowering agents (HMG-CoA-reductase inhibitors), but fenofibrate treatment elevated the plasma l-arginine:ADMA ratio, suggesting an improvement of endogenous NO formation and endothelial function. The results do not support the view that in vivo ADMA metabolism itself is directly influenced by cholesterol or homocysteine.

      Abbreviations:

      ADMA (asymmetrical dimethylarginine), DDAH (dimethylarginine dimethylaminohydrolse), tHcy (total homocysteine (sum of free- and protein-bound homocysteine)), GFR (glomerular filtration rate), HDL-C (high density lipoprotein cholesterol), LDL-C (low density lipoprotein cholesterol), PLP (pyridoxal 5-phosphate), HPLC (high performance liquid chromatography), eNOS (endothelial nitric oxide synthase), NO (nitric oxide), PPAR (peroxisome proliferator activating receptor)

      Keywords

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