Aging-Induced Phenotypic Changes and Oxidative Stress Impair Coronary Arteriolar Function

• Published in: Circulation research 2002-06, Vol.90 (11), p.1159-1166
• Main Authors: Csiszar, Anna, Ungvari, Zoltan, Edwards, John G., Kaminski, Pawel, Wolin, Michael S., Koller, Akos, Kaley, Gabor
• Format: Article
• Language: English
• Subjects: 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt - pharmacology; Aging - physiology; Animals; Arginine - pharmacology; Arterioles - drug effects; Arterioles - metabolism; Arterioles - physiology; Biological and medical sciences; Blotting, Western; Bridged Bicyclo Compounds, Heterocyclic; Coronary Vessels - drug effects; Coronary Vessels - metabolism; Coronary Vessels - physiology; Enzyme Inhibitors - pharmacology; Fatty Acids, Unsaturated; Fundamental and applied biological sciences. Psychology; Heart; Hydrazines - pharmacology; Immunohistochemistry; In Vitro Techniques; Male; Multienzyme Complexes - metabolism; NADH, NADPH Oxidoreductases - metabolism; NG-Nitroarginine Methyl Ester - pharmacology; Nitrates - blood; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase - metabolism; Nitrites - blood; Oxidative Stress - physiology; Phenotype; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Superoxide Dismutase - metabolism; Superoxide Dismutase - pharmacology; Tyrosine - analogs & derivatives; Tyrosine - metabolism; Vasodilation - drug effects; Vertebrates: cardiovascular system; Xanthine Oxidase - metabolism
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.0000020401.61826.ea

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 (Y41±8% versus A3±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 p47, p67, Mox-1, and p22 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.