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1 Department of Integrative Physiology, University of Colorado, Boulder, CO, USA2 Department of Medicine, Divisions of Cardiology and Geriatric Medicine, University of Colorado Health Sciences Center, Denver, CO, USA
Peripheral conduit artery flow-mediated dilatation decreases with ageing in humans. The underlying mechanisms and efficacy of preventive strategies are unknown. Brachial artery flow-mediated dilatation was determined at baseline and after ascorbic acid (vitamin C) intravenous infusion and chronic supplementation (500 mg day–1 for 30 days) in three groups of healthy men: young sedentary (n= 11; 25 ± 1 years, mean ±S.E.M.), older sedentary (n= 9; 64 ± 2), and older endurance-exercise trained (n= 9; 64 ± 2). At baseline, flow-mediated dilatation (normalized for the hyperaemic stimulus) was 
45% lower in the older (0.015 ± 0.001) versus young (0.028 ± 0.004) sedentary men (P < 0.01), but was preserved in older exercising men (0.028 ± 0.004). Ascorbic acid infusion increased plasma concentrations > 15-fold in all groups and restored flow-mediated dilatation in the sedentary older men (to 0.023 ± 0.002; P > 0.1 versus other groups), with no effects in the other two groups. Oral ascorbic acid supplementation did not affect flow-mediated dilatation in any group. Brachial artery endothelium-independent dilatation (sublingual nitroglycerin) did not differ among the groups at baseline nor change with ascorbic acid administration. These results provide the first evidence for an important role of oxidative stress in both the impairment in peripheral conduit artery flow-mediated dilatation with sedentary human ageing and the preservation of flow-mediated dilatation with physically active ageing.
(Received 21 October 2003;
accepted after revision 23 January 2004;
first published online 30 January 2004)
Corresponding author D. R. Seals: Department of Integrative Physiology, University of Colorado at Boulder, UCB 354, Boulder, CO 80309, USA. Email: seals{at}spot.colourado.edu
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