Correction of endothelial dysfunction in chronic heart failure: additional effects of exercise training and oral L-arginine supplementation

OBJECTIVES The aim of this study was to analyze whether L-arginine (L-arg.) has comparable or additive effects to physical exercise regarding endothelium-dependent vasodilation in patients with chronic heart failure (CHF). BACKGROUND Endothelial dysfunction in patients with CHF can be corrected by both dietary supplementation with L-arg. and regular physical exercise. METHODS Forty patients with severe CHF (left ventricular ejection fraction 19 ± 9%) were randomized to an L-arg. group (8 g/day), a training group (T) with daily handgrip training, L-arg. and T (L-arg. + T) or an inactive control group (C). The mean internal radial artery diameter was determined at the beginning and after four weeks in response to brachial arterial administration of acetylcholine (ACh) (7.5, 15, 30 μg/min) and nitroglycerin (0.2 mg/min) with a transcutaneous high-resolution 10 MHz A-mode echo tracking system coupled with a Doppler device. The power of the study to detect clinically significant differences in endothelium-dependent vasodilation was 96.6%. RESULTS At the beginning, the mean endothelium-dependent vasodilation in response to ACh, 30 μg/min was 2.54 ± 0.09% (p = NS between groups). After four weeks, internal radial artery diameter increased by 8.8 ± 0.9% after ACh 30 μg/min in L-arg. (p < 0.001 vs. C), by 8.6 ± 0.9% in T (p < 0.001 vs. C) and by 12.0 ± 0.3% in L-arg. + T (p < 0.005 vs. C, L-arg. and T). Endothelium-independent vasodilation as assessed by infusion of nitroglycerin was similar in all groups at the beginning and at the end of the study. CONCLUSIONS Dietary supplementation of L-arg. as well as regular physical exercise improved agonist-mediated, endothelium-dependent vasodilation to a similar extent. Both interventions together seem to produce additive effects with respect to endothelium-dependent vasodilation.