Aging impairs flow-induced dilation in coronary arterioles: role of NO and H(2)O(2)

Am J Physiol Heart Circ Physiol. 2009 Sep;297(3):H1087-95. doi: 10.1152/ajpheart.00356.2009. Epub 2009 Jul 17.


Aging contributes significantly to the development of cardiovascular disease and is associated with elevated production of reactive oxygen species (ROS). The beneficial effects of nitric oxide (NO)-mediated vasodilation are quickly abolished in the presence of ROS, and this effect may be augmented with aging. We previously demonstrated an age-induced impairment of flow-induced dilation in rat coronary arterioles. Therefore, the purpose of this study was to determine the effects of O(2)(-) scavenging, as well as removal of H(2)O(2), the byproduct of O(2)(-) scavenging, on flow-mediated dilation in coronary resistance arterioles of young (4 mo) and old (24 mo) male Fischer 344 rats. Flow increased NO and H(2)O(2) production as evidenced by enhanced diaminofluorescein and dichlorodihydrofluorescein fluorescence, respectively, whereas aging reduced flow-induced NO and H(2)O(2) production. Endothelium-dependent vasodilation was evaluated by increasing intraluminal flow (5-60 nl/s) before and after treatment with the superoxide dismutase mimetic Tempol (100 muM), the H(2)O(2) scavenger catalase (100 U/ml), or Tempol plus catalase. Catalase reduced flow-induced dilation in both groups, whereas Tempol and Tempol plus catalase diminished vasodilation in young but not old rats. Tempol plus deferoxamine (100 muM), an inhibitor of hydroxyl radical formation, reversed Tempol-mediated impairment of flow-induced vasodilation in young rats and improved flow-induced vasodilation in old rats compared with control. Immunoblot analysis revealed increases in endogenous superoxide dismutase, catalase, and nitrotyrosine protein levels with aging. Collectively, these data indicate that NO- and H(2)O(2)-mediated flow-induced signaling decline with age in coronary arterioles and that elevated hydroxyl radical formation contributes to the age-related impairment of flow-induced vasodilation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Antioxidants / pharmacology
  • Arterioles / metabolism
  • Catalase / metabolism
  • Catalase / pharmacology
  • Coronary Circulation / drug effects
  • Coronary Circulation / physiology*
  • Cyclic N-Oxides / pharmacology
  • Deferoxamine / pharmacology
  • Hydrogen Peroxide / metabolism*
  • Male
  • Microscopy, Fluorescence
  • Nitric Oxide / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred F344
  • Reactive Oxygen Species / metabolism
  • Siderophores / pharmacology
  • Spin Labels
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism
  • Vasodilation / drug effects
  • Vasodilation / physiology*


  • Antioxidants
  • Cyclic N-Oxides
  • RNA, Messenger
  • Reactive Oxygen Species
  • Siderophores
  • Spin Labels
  • Nitric Oxide
  • 3-nitrotyrosine
  • Tyrosine
  • Hydrogen Peroxide
  • Catalase
  • Superoxide Dismutase
  • Deferoxamine
  • tempol