title: Xanthine oxidase does not contribute to impaired peripheral conduit artery endothelium-dependent dilatation with ageing.
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.
authors.affiliation: Department of Integrative Physiology, University of Colorado at Boulder, UCB 354, Boulder, CO 80309, USA. eskurza@colourado.edu
authors.forename: Iratxe
authors.initials: I
authors.lastname: Eskurza
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Kahn
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Seals
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging; D000493:Allopurinol / Q000494:pharmacology; D001783:Blood Flow Velocity; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000201:enzymology / Q000503:physiopathology*; D018592:Cross-Over Studies; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D008875:Middle Aged; D014463:Ultrasonography; D014664:Vasodilation; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D000493:Allopurinol; D014969:Xanthine Oxidase