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Xanthine oxidase does not contribute to oxidative stress‐mediated impairment in endothelium‐dependent dilation with age
Author(s) -
Kahn Zachary D.,
Seals Douglas R.,
Eskurza Iratxe
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1179-b
Subject(s) - xanthine oxidase , oxidative stress , medicine , uric acid , endothelium , brachial artery , allopurinol , endocrinology , endothelial dysfunction , reactive oxygen species , hyperuricemia , chemistry , biochemistry , enzyme , blood pressure
Increased vascular oxidative stress is the key mechanism involved in the age‐related decline in endothelium‐dependent dilation (EDD). We tested the hypothesis that xanthine oxidase (XO), a major vascular source of reactive oxygen species, contributes to oxidative stress‐mediated impairment in EDD with age. At baseline, brachial artery flow‐mediated dilation (FMD) was 55% lower in older (n=9, 64±2 years, 8M/1F, mean±SE) vs. young (n=9, 26±1 years, 8M/1F) healthy sedentary adults (3.41±0.44 vs. 7.53±0.67%, P<0.001), whereas endothelium‐independent brachial dilation (EID; sublingual nitroglycerin) did not differ between groups. Oxidized low‐density lipoprotein (oxi‐LDL), a measure of systemic oxidative stress, was greater at baseline in the older vs. young subjects (53.3± 5.9 vs. 46.8±2.4 U/L, 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<0.01), but did not affect FMD, EID, or oxi‐LDL in either group. Vascular endothelial expression of XO protein (immunofluorescence) was not different in antecubital vein cells from the young and older subjects (0.56±0.12 vs. 0.68±0.19, P=0.49). We conclude that XO does not contribute to oxidative‐stress mediated impairment in EDD with age in healthy adult humans, possibly because of an absence of age‐associated up‐regulation of endothelial XO. Supported by NIH AG006537 , AG013038 , and AG022241.