Fenofibrate increases the L-arginine:ADMA ratio by increase of L-arginine concentration but has no effect on ADMA concentration.
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.
Dierkes
Jutta
J
Institute of Clinical Chemistry and Biochemistry, University Hospital, Leipziger Str. 44, D-39120 Magdeburg, Germany. jutta.dierkes@medizin.uni-magdeburg.de
Westphal
Sabine
S
Martens-Lobenhoffer
Jens
J
Luley
Claus
C
Bode-Böger
Stefanie M
SM
D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000187:drug effects / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D011345:Fenofibrate / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006801:Humans; D006949:Hyperlipidemias / Q000175:diagnosis / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome
D015415:Biomarkers; D000960:Hypolipidemic Agents; C018524:N,N-dimethylarginine; D001120:Arginine; D011345:Fenofibrate