Circulation Research. 2002
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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Submitted on January 17, 2002
Revised on April 22, 2002
Accepted on April 22, 2002
Aging-Induced Phenotypic Changes and Oxidative Stress Impair Coronary Arteriolar Function
Anna Csiszar ;
From the Department of Physiology, New York Medical College, Valhalla, NY.
* To whom correspondence should be addressed. E-mail: gabor_kaley{at}nymc.edu.
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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