title: Aging-induced phenotypic changes and oxidative stress impair coronary arteriolar function.
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 TXA(2) receptor antagonist SQ29,548). For lucigenin chemiluminescence, O(2)(.-) generation was significantly greater in A than Y vessels and could be inhibited with SOD and diphenyliodonium. NADH-driven O(2)(.-) generation was also greater in A vessels. Both endothelial and smooth muscle cells of A vessels produced O(2)(.-) (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(phox), p67(phox), Mox-1, and p22(phox) 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.
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, NY, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Csiszar
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Ungvari
authors.forename: John G
authors.initials: JG
authors.lastname: Edwards
authors.forename: Pawel
authors.initials: P
authors.lastname: Kaminski
authors.forename: Michael S
authors.initials: MS
authors.lastname: Wolin
authors.forename: Akos
authors.initials: A
authors.lastname: Koller
authors.forename: Gabor
authors.initials: G
authors.lastname: Kaley
mesh_terms: D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015153:Blotting, Western; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress / Q000502:physiology*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D009097:Multienzyme Complexes; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C002744:3-nitrotyrosine; D014443:Tyrosine; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; C045749:SQ 29548; D001120:Arginine; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester