An age-related decline in endothelial function is not associated with alterations in L-arginine transport in humans.
OBJECTIVE
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 Throughout 40 min of intra-arterial (i.a.) infusion of [3H]L-arginine (100 nCi/min), venous blood samples were withdrawn for the determination of L-arginine clearance.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 microg/min) and sodium nitroprusside (SNP; 2 and 8 microg/min).


RESULTS
While ACh-induced vasodilation decreased with age (37 microg/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 [3H]L-arginine clearance (young 126.08 +/- 19.05, middle-aged 122.47 +/- 20.96, older 126.56 +/- 19.56 ml/min; NS). Further [3H]L-arginine uptake studies in isolated peripheral blood mononuclear cells supported our in vivo findings, demonstrating no difference in [3H]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.
Ahlers
Belinda A
BA
Alfred and Baker Medical Unit, Wynn Department of Metabolic Cardiology, Baker Heart Research Institute, Melbourne, Australia.
Parnell
Melinda M
MM
Chin-Dusting
Jaye P F
JP
Kaye
David M
DM
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000375:Aging / Q000097:blood / Q000502:physiology*; D001120:Arginine / Q000097:blood*; D001692:Biological Transport / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010991:Plethysmography; D012016:Reference Values; D014664:Vasodilation / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D001120:Arginine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine