Asymmetric Dimethylarginine Determines the Improvement of Endothelium-Dependent Vasodilation by SimvastatinEffect of Combination With Oral L-Arginine
Gerhild I. Böger, PhD*,
Tanja K. Rudolph, MD*, ,
Renke Maas, MD*,
Edzard Schwedhelm, PhD*,
Ekaterina Dumbadze*,
Anneke Bierend*,
Ralf A. Benndorf, MD* and
Rainer H. Böger, MD*,*
* Clinical Pharmacology Unit, Institute of Experimental and Clinical Pharmacology, Hamburg, Germany
Department of Cardiology, University Heart Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
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Figure 1 Distribution of Circulating ADMA Concentrations
(A) Distribution of circulating asymmetric dimethylarginine (ADMA) concentrations in a cohort of 98 clinically healthy ambulatory subjects. Vertical lines indicate the median (solid line), which was 0.39 µmol/l, and the 25th and 75th percentiles (dashed lines; 0.35 µmol/l and 0.48 µmol/l, respectively). (B) Asymmetric dimethylarginine levels in study participants. Mean and SD in the 2 groups are marked by a horizontal bar and vertical line, respectively. Each subject is represented by a circle. In panel B, filled circles indicate subjects with high ADMA and unfilled circles indicate subjects with low ADMA.
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Figure 2 Effects of Simvastatin, L-Arginine, and Their Combination on Endothelium-Dependent and -Independent Vasodilation in Subjects With High ADMA
Endothelium-dependent (A) and endothelium-independent vasodilation (B) in the brachial artery as assessed by high-resolution ultrasound before and after 3 weeks of treatment with simvastatin, L-arginine sustained release (SR), or their combination, in subjects with elevated asymmetric dimethylarginine (ADMA) concentration. *p < 0.05 versus baseline or between groups as indicated. Hatched bars = before treatment; black bars = after treatment. GTN = nitroglycerin; n.s. = not significant.
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Figure 3 Effects of Simvastatin, L-Arginine, and Their Combination on Endothelium-Dependent and -Independent Vasodilation in Subjects With Low ADMA
Endothelium-dependent (A) and endothelium-independent vasodilation (B) in the brachial artery as assessed by high-resolution ultrasound before and after 3 weeks of treatment with simvastatin, L-arginine SR, or their combination, in subjects with low-normal ADMA concentration. *p < 0.05 versus baseline or between groups as indicated. Hatched bars = before treatment; black bars = after treatment. Abbreviations as in Figure 2.
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Figure 4 Relationship Between Plasma ADMA Concentration and the Endothelial Response to Simvastatin
Filled circles = subjects with high ADMA; unfilled circles = subjects with low ADMA. ADMA = asymmetric dimethylarginine; FMD = flow-mediated dilation.
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