Acute administration of allopurinol did not affect flow-mediated dilatation, despite baseline FMD being 55% lower in older versus young adults (3.41% vs 7.53%, P<0.001).
Cross-Sectional (n=18)
Does acute administration of allopurinol improve brachial artery flow-mediated dilatation in older healthy adults?
Xanthine oxidase does not appear to contribute to the age-related decline in peripheral conduit artery endothelium-dependent dilatation in humans.
Absolute Event Rate: 3.41% vs 7.53%
p-value: p=<0.001
Vascular oxidative stress is the key mechanism involved in the age-related decline in endothelium-dependent dilatation (EDD). We tested the hypothesis that xanthine oxidase (XO), a major vascular source of reactive oxygen species, contributes to the impairment in EDD with ageing. At baseline, brachial artery flow-mediated dilatation (FMD) was 55% lower in older (n = 9, 64 +/- 2 years, 8M/1F, mean +/- S.E.M.) versus young (n = 9, 26 +/- 1 years, 8M/1F) healthy adults (3.41 +/- 0.44 versus 7.53 +/- 0.67%, P < 0.001), whereas endothelium-independent dilatation (EID; sublingual nitroglycerin) did not differ between groups. Plasma oxidized low-density lipoprotein (oxi-LDL), a measure of systemic oxidative stress, was greater at baseline in the older subjects (58.3 +/- 5.9 versus 46.8 +/- 2.4 U l(-1), P < 0.05) and inversely correlated with baseline FMD (r = - 0.54; P < 0.05). Acute administration of allopurinol, a competitive inhibitor of XO, reduced plasma uric acid concentrations similarly in both groups (P < 0.001), but did not affect FMD, EID, or oxi-LDL in either group. Vascular endothelial protein expression of XO (immunofluorescence) was not different in antecubital venous cells from the young and older subjects (0.56 +/- 0.12 versus 0.68 +/- 0.19 XO intensity/human umbilical vein endothelial cell intensity, P = 0.49). We conclude that XO does not contribute to oxidative stress-associated reductions in peripheral conduit artery EDD with ageing in humans, possibly due to an absence of age-associated up-regulation of endothelial XO.
Eskurza et al. (Fri,) conducted a cross-sectional in Age-related decline in endothelium-dependent dilatation (n=18). Allopurinol vs. Young adults (baseline comparison) was evaluated on Baseline brachial artery flow-mediated dilatation (FMD) (p=<0.001). Acute administration of allopurinol did not affect flow-mediated dilatation, despite baseline FMD being 55% lower in older versus young adults (3.41% vs 7.53%, P<0.001).
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