Effect of high-dose statin treatment on plasma concentrations of endogenous nitric oxide synthase inhibitors.
Asymmetric dimethylarginine (ADMA) and monomethylarginine (LMMA) are endogenous inhibitors of nitric oxide synthase. A high level of ADMA in plasma has shown to be a significant risk factor for acute coronary syndromes and elevated plasma ADMA levels are prevalent in patients with hypercholesterolemia. It was therefore hypothesized that lowering plasma cholesterol levels with statin treatment would also lower ADMA concentrations. This double-blind study addressed the effect of high-dose statin treatment on plasma levels of ADMA and LMMA. Forty-eight subjects with mild hypercholesterolemia were randomly assigned to receive simvastatin 80 mg/d, atorvastatin 40 mg/d, or placebo for 8 weeks. Both statins decreased low-density lipoprotein cholesterol effectively (simvastatin 54% and atorvastatin 49%). However, concentrations of arginine derivatives remained unchanged during statin treatment and did not correlate with cholesterol levels. This study indicates that statin treatment has no clear influence on plasma ADMA or LMMA concentrations.
Päivä
Hannu
H
Department of Internal Medicine, Tampere University Hospital, Tampere, Finland. hannu.paiva@uta.fi
Laakso
Juha
J
Lehtimäki
Terho
T
Isomustajärvi
Marja
M
Ruokonen
Inkeri
I
Laaksonen
Reijo
R
D000368:Aged; D000704:Analysis of Variance; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D001391:Azo Compounds / Q000097:blood / Q000494:pharmacology; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000097:blood* / Q000494:pharmacology; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D001391:Azo Compounds; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C077182:monomethylarginine di-(4-hydroxyazobenzene-4'-sulfonate); C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase