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Clinical Trial
. 2006 Mar 15;571(Pt 3):661-8.
doi: 10.1113/jphysiol.2005.102566. Epub 2006 Jan 26.

Xanthine oxidase does not contribute to impaired peripheral conduit artery endothelium-dependent dilatation with ageing

Iratxe Eskurza  1 , Zachary D Kahn, Douglas R Seals
Affiliations
Clinical Trial

Xanthine oxidase does not contribute to impaired peripheral conduit artery endothelium-dependent dilatation with ageing

Iratxe Eskurza et al. J Physiol. .

Abstract

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.

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Figures

Figure 1
Figure 1
Endothelium-dependent and -independent dilatation during baseline placebo conditions and in response to acute allopurinol administration Brachial artery flow-mediated dilatation (FMD) (top panel) and endothelium independent dilatation (EID) (bottom panel) in young (filled bars) and older (open bars) adults after acute oral placebo or allopurinol administration. FMD was lower in the older adults under both conditions, but EID was not different between groups in either condition. Allopurinol had no effect on FMD or EID in either group. Means ± s.e.m. are shown. *P < 0.001 versus young adults.
Figure 2
Figure 2. Relations between endothelium-dependent dilatation and systemic oxidative stress
Brachial artery FMD under baseline placebo conditions was inversely related to plasma oxidized-LDL concentrations in the pooled sample (A) and among older adults (B).
See this image and copyright information in PMC

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