title: Enhanced peroxynitrite formation is associated with vascular aging.
abstract: Vascular aging is mainly characterized by endothelial dysfunction. We found decreased free nitric oxide (NO) levels in aged rat aortas, in conjunction with a sevenfold higher expression and activity of endothelial NO synthase (eNOS). This is shown to be a consequence of age-associated enhanced superoxide (.O(2)(-)) production with concomitant quenching of NO by the formation of peroxynitrite leading to nitrotyrosilation of mitochondrial manganese superoxide dismutase (MnSOD), a molecular footprint of increased peroxynitrite levels, which also increased with age. Thus, vascular aging appears to be initiated by augmented.O(2)(-) release, trapping of vasorelaxant NO, and subsequent peroxynitrite formation, followed by the nitration and inhibition of MnSOD. Increased eNOS expression and activity is a compensatory, but eventually futile, mechanism to counter regulate the loss of NO. The ultrastructural distribution of 3-nitrotyrosyl suggests that mitochondrial dysfunction plays a major role in the vascular aging process.
authors: Division of Cardiology, University Hospital, 8091 Zurich, Switzerland.
authors: B
authors: B
authors: van der Loo
authors: R
authors: R
authors: Labugger
authors: J N
authors: JN
authors: Skepper
authors: M
authors: M
authors: Bachschmid
authors: J
authors: J
authors: Kilo
authors: J M
authors: JM
authors: Powell
authors: M
authors: M
authors: Palacios-Callender
authors: J D
authors: JD
authors: Erusalimsky
authors: T
authors: T
authors: Quaschning
authors: T
authors: T
authors: Malinski
authors: D
authors: D
authors: Gygi
authors: V
authors: V
authors: Ullrich
authors: T F
authors: TF
authors: Lüscher
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D001835:Body Weight; D000001:Calcimycin / Q000494:pharmacology; D016922:Cellular Senescence / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004790:Enzyme Induction; D006439:Hemodynamics; D008297:Male; D016253:Microscopy, Immunoelectron; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D018384:Oxidative Stress; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
chemical_list: D009566:Nitrates; D013481:Superoxides; D009599:Nitroprusside; C039642:peroxynitric acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D000001:Calcimycin; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D000109:Acetylcholine