期刊
CIRCULATION RESEARCH
卷 90, 期 11, 页码 1159-1166出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.RES.0000020401.61826.EA
关键词
arteriole; endothelium; superoxide; reactive oxygen species; free radical scavenger
资金
- NHLBI NIH HHS [P01 HL043023, HL-46813, HL-59417] Funding Source: Medline
- PHS HHS [P0 43023] Funding Source: Medline
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.
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