An age-related decline in endothelial function is not associated with alterations in L-arginine transport in humans.

Objectives Endothelial dysfunction is established in aged individuals; however, the mechanism(s) are not fully elucidated. We have previously identified L-arginine transport as a potential rate-limiting factor in nitric oxide (NO) production in heart-failure patients, characterized with endothelial dysfunction. We therefore aimed to investigate whether the age-related decline in endothelial function is due to reduced transport of the NO precursor, L-arginine. Methods Thirty-seven healthy males aged between 19 and 69 were recruited. Throughout 40 min of intra-arterial (i.a.) infusion of [ 3 H]L-arginine (100 nCi/min), venous blood samples were withdrawn for the determination of L-arginine clearance. Venous occlusion plethysmography was then used to record the forearm blood flow responses to i.a. infusions of acetylcholine (ACh; 9.25 and 37 μg/min) and sodium nitroprusside (SNP; 2 and 8 μg/min). Results While ACh-induced vasodilation decreased with age (37 μg/min; young 15.87 ± 1.30, middle-aged 9.59 ± 1.33, older 10.42 ± 1.12 ml/min per 100 ml tissue; P= 0.001), there was no change in forearm [ 3 H]L-arginine clearance (young 126.08 ± 19.05, middle-aged 122.47 ± 20.96, older 126.56 ± 19.56 ml/min; NS). Further [ 3 H]L-arginine uptake studies in isolated peripheral blood mononuclear cells supported our in vivo findings, demonstrating no difference in [ 3 H]L-arginine transport across the age spectrum. Conclusions The present study excludes the hypothesis of impaired L-arginine transport as a potential mechanism for the age-related decline in endothelial function.