Plasma asymmetric dimethylarginine modifies the effect of pravastatin on myocardial blood flow in young adults.
Elevated plasma levels of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) are related to decreased myocardial vasodilatory capacity and increased risk of acute coronary events. As statin treatment is known to increase nitric oxide bioavailability and enhance myocardial function, we tested whether ADMA concentration modifies the effect of pravastatin on myocardial blood flow in young adults with mild hypercholesterolemia. Fifty-one men (35 +/- 4 years) were randomly assigned to receive either pravastatin (40 mg/day) or placebo for 6 months. Myocardial blood flow was measured at rest and during adenosine-induced hyperemia using positron emission tomography and oxygen-15-labeled water at baseline and after treatment. Plasma ADMA levels were assessed with high performance liquid chromatography. Low baseline plasma ADMA concentration (< median) predicted a significant improvement of adenosine-induced blood flow after statin intervention (baseline to follow-up change +35%, p = 0.004), whereas high baseline ADMA (> or = median) was associated with no increase in adenosine-induced flow.
Janatuinen
Tuula
T
Turku PET Centre, University of Turku, Finland.
Laakso
Juha
J
Laaksonen
Reijo
R
Vesalainen
Risto
R
Nuutila
Pirjo
P
Lehtimäki
Terho
T
Raitakari
Olli T
OT
Knuuti
Juhani
J
D000241:Adenosine / Q000494:pharmacology; D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D001783:Blood Flow Velocity / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000097:blood*; D006801:Humans; D006940:Hyperemia / Q000139:chemically induced; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D017035:Pravastatin / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D014055:Tomography, Emission-Computed
D000924:Anticholesteremic Agents; D004791:Enzyme Inhibitors; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000241:Adenosine; D017035:Pravastatin