Antioxidants inhibit angiogenesis in vivo through down-regulation of nitric oxide synthase expression and activity.
Although reactive oxygen species (ROS) participate in many cellular mechanisms, only few data exist concerning their involvement in physiological angiogenesis. The aim of the present work was to elucidate possible mechanisms through which ROS affect angiogenesis in vivo, using the model of the chicken embryo chorioallantoic membrane (CAM). Superoxide dismutase (SOD) and its membrane permeable mimetic tempol, dose dependently decreased angiogenesis and down-regulated inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production. The NADPH oxidase inhibitors, 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF) and apocynin, but not allopurinol, also had a dose dependent inhibitory effect on angiogenesis and NO production in vivo. Catalase and the intracellular hydrogen peroxide (H2O2) scavenger sodium pyruvate decreased, while H2O2 increased in a dose-dependent manner the number of CAM blood vessels, as well as the expression and activity of iNOS. Dexamethasone, which down-regulated NO production by iNOS and L-NAME, but not D-NAME, dose dependently decreased angiogenesis in vivo. These data suggest that antioxidants affect physiological angiogenesis in vivo, through regulation of NOS expression and activity.
Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, Patras, GR 26504, Greece.
Christos
C
Polytarchou
Evangelia
E
Papadimitriou
D000482:Allantois / Q000201:enzymology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D002462:Cell Membrane / Q000201:enzymology; D002642:Chick Embryo; D002823:Chorion / Q000201:enzymology*; D003497:Cyclic N-Oxides / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013113:Spin Labels; D013450:Sulfones / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D013113:Spin Labels; D013450:Sulfones; D009569:Nitric Oxide; C002010:4-(2-aminoethyl)benzenesulfonylfluoride; D003907:Dexamethasone; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester