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Vascular Medicine
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Plasma asymmetric dimethylarginine modifies the effect of pravastatin on myocardial blood flow in young adults

Tuula Janatuinen

Turku PET Centre, University of Turku, Finland

Juha Laakso

Department of Clinical Pharmacology, University of Helsinki, Finland

Reijo Laaksonen

Department of Clinical Pharmacology, University of Helsinki, Finland, Department of Medicine, University of Tampere, Finland

Risto Vesalainen

Turku PET Centre, University of Turku, Finland, Department of Medicine, University of Turku, Finland

Pirjo Nuutila

Turku PET Centre, University of Turku, Finland, Department of Medicine, University of Turku, Finland

Terho Lehtimäki

Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, University Hospital of Tampere and Tampere University Medical School, Tampere, Finland

Olli T Raitakari

Turku PET Centre, University of Turku, Finland

Juhani Knuuti

Turku PET Centre, University of Turku, Finland, juhani.knuuti{at}utu.fi

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 modi-fies 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 (≥ median) was associated with no increase in adenosine-induced flow.

Key Words: asymmetric dimethylarginine • blood flow • positron emission tomography • pravastatin

Vascular Medicine, Vol. 8, No. 3, 185-189 (2003)
DOI: 10.1191/1358863x03vm490oa
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