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.

. Ascorbic acid does not affect large elastic artery compliance or central blood pressure in young and older men. Am J Physiol Heart Circ Physiol 286: H1528-H1534, 2004; 10.1152/ ajpheart.00879.2003.-Large elastic artery compliance is reduced and arterial blood pressure (BP) is increased in the central (cardiothoracic) circulation with aging. Reactive oxygen species may tonically modulate central arterial compliance and BP in humans, and oxidative stress may contribute to adverse changes with aging. If so, antioxidant administration may have beneficial effects. Young (Y; 26 Ϯ 1 yr, mean Ϯ SE) and older (O; 63 Ϯ 2 yr, mean Ϯ SE) healthy men were studied at baseline and during acute (intravenous infusion; Y: n ϭ 13, O: n ϭ 12) and chronic (500 mg/day for 30 days; Y: n ϭ 10, O: n ϭ 10) administration of ascorbic acid (vitamin C). At baseline, peripheral (brachial artery) BP did not differ in the two groups, but carotid artery compliance was 43% lower (1.2 Ϯ 0.1 vs. 2.1 Ϯ 0.1 mm 2 /mmHg ϫ 10 Ϫ1 , P Ͻ 0.01) and central (carotid) BP (systolic: 116 Ϯ 5 vs. 101 Ϯ 3 mmHg, P Ͻ 0.05, and pulse pressure: 43 Ϯ 4 vs. 36 Ϯ 3 mmHg, P ϭ 0.16), carotid augmentation index (AIx; 27.8 Ϯ 7.8 vs. Ϫ20.0 Ϯ 6.6%, P Ͻ 0.001), and aortic pulse wave velocity (PWV; 950 Ϯ 88 vs. 640 Ϯ 38 cm/s, P Ͻ 0.01) were higher in the older men. Plasma ascorbic acid concentrations did not differ at baseline (Y: 71 Ϯ 5 vs. O: 61 Ϯ 7 mol/l, P ϭ 0.23), increased (P Ͻ 0.001) to supraphysiological levels during infusion (Y: 1,240 Ϯ 57 and O: 1,056 Ϯ 83 mol/l), and were slightly elevated (P Ͻ 0.001 vs. baseline) with supplementation (Y: 96 Ϯ 5 mol/l vs. O: 85 Ϯ 6). Neither ascorbic acid infusion nor supplementation affected peripheral BP, heart rate, carotid artery compliance, central BP, carotid AIx, or aortic PWV (all P Ͼ 0.26). These results indicate that the adverse changes in large elastic artery compliance and central BP with aging in healthy men are not 1) mediated by ascorbic acid-sensitive oxidative stress (infusion experiments) and 2) affected by short-term, moderate daily ascorbic acid (vitamin C) supplementation. arterial stiffness; vitamin C; antioxidants; human aging ONE OF THE MOST physiologically and clinically important changes that occurs with cardiovascular (CV) aging is a progressive reduction in the compliance (increase in stiffness) of the large elastic arteries in the central (i.e., cardiothoracic) circulation (e.g., the proximal aorta and carotid artery) (33,35,50). This process leads to several potentially adverse changes in CV structure and function including increases in central arterial blood pressure (BP), arterial intima-media thickening, increases in aortic impedance, left ventricular remodeling, reduced diastolic function, and decreased baroreflex responsiveness (28,34,35,43,44,50). Indeed, reduced large elastic artery compliance is an independent risk factor for future CV disease (CVD) (25,32).Structural changes in the extracellular matrix of the vascular wall including increases in collagen content and cross-linking as well as...