Circulation Research. 2002;90:1159-1166
Published online before print May 2, 2002, doi: 10.1161/01.RES.0000020401.61826.EA
Published online before print May 2, 2002, doi: 10.1161/01.RES.0000020401.61826.EA
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© 2002 American Heart Association, Inc.
Integrative Physiology |
Aging-Induced Phenotypic Changes and Oxidative Stress Impair Coronary Arteriolar Function
From the Department of Physiology, New York Medical College, Valhalla, NY.
Correspondence to Gabor Kaley, PhD, Dept of Physiology, New York Medical College, Valhalla, NY 10595. E-mail gabor_kaley@ nymc.edu
Abstract— 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 TXA2 receptor 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 p22phox did 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.
Key Words: arteriole • endothelium • superoxide • reactive oxygen species • free radical scavenger
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