Aging-Induced Phenotypic Changes and Oxidative Stress Impair Coronary Arteriolar Function
作者:
Anna Csiszar,
Zoltan Ungvari,
John Edwards,
Pawel Kaminski,
Michael Wolin,
Akos Koller,
Gabor Kaley,
期刊:
Circulation Research: Journal of the American Heart Association
(OVID Available online 2002)
卷期:
Volume 90,
issue 11
页码: 1159-1166
ISSN:0009-7330
年代: 2002
出版商: OVID
关键词: arteriole;endothelium;superoxide;reactive oxygen species;free radical scavenger
数据来源: OVID
摘要:
We aimed to elucidate the possible role of phenotypic alterations and oxidative stress in age-related endothelial dysfunction of coronary arterioles. Arterioles were isolated from the hearts of young adult (Y, 14 weeks) and aged (A, 80 weeks) male Sprague-Dawley rats. For videomicroscopy, pressure-induced tone of Y and A arterioles and their passive diameter did not differ significantly. In A, arterioles L-NAME (a NO synthase blocker)–sensitive flow-induced dilations were significantly impaired (Y: 41±8% versus A: 3±2%), which could be augmented by superoxide dismutase (SOD) or Tiron (but not l-arginine or the TXA2receptor antagonist SQ29,548). For lucigenin chemiluminescence, O2·−generation was significantly greater in A than Y vessels and could be inhibited with SOD and diphenyliodonium. NADH-driven O2·−generation was also greater in A vessels. Both endothelial and smooth muscle cells of A vessels produced O2·−(shown with ethidium bromide fluorescence). For Western blotting, expression of eNOS and COX-1 was decreased in A compared with Y arterioles, whereas expressions of COX-2, Cu/Zn-SOD, Mn-SOD, xanthine oxidase, and the NAD(P)H oxidase subunits p47phox, p67phox, Mox-1, and p22phoxdid not differ. Aged arterioles showed an increased expression of iNOS, confined to the endothelium. Decreased eNOS mRNA and increased iNOS mRNA expression in A vessels was shown by quantitative RT-PCR. In vivo formation of peroxynitrite was evidenced by Western blotting, and immunohistochemistry showing increased 3-nitrotyrosine content in A vessels. Thus, aging induces changes in the phenotype of coronary arterioles that could contribute to the development of oxidative stress, which impairs NO-mediated dilations.
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