title: Poly(ADP-ribose) polymerase-1 protects from oxidative stress induced endothelial dysfunction.
abstract: BACKGROUND
  Generation of reactive oxygen species (ROS) is a key feature of vascular disease. Activation of the nuclear enzyme poly (adenosine diphosphate [ADP]-ribose) polymerase-1 (PARP-1) is a downstream effector of oxidative stress.
  
  
  METHODS
  PARP-1(-/-) and PARP-1(+/+) mice were injected with paraquat (PQ; 10 mg/kg i.p.) to induce intracellular oxidative stress. Aortic rings were suspended in organ chambers for isometric tension recording to analyze vascular function.
  
  
  RESULTS
  PQ treatment markedly impaired endothelium-dependent relaxations to acetylcholine in PARP-1(-/-), but not PARP-1(+/+) mice (p<0.0001). Maximal relaxation was 45% in PQ treated PARP-1(-/-) mice compared to 79% in PARP-1(+/+) mice. In contrast, endothelium-independent relaxations to sodium nitroprusside (SNP) were not altered. After PQ treatment, l-NAME enhanced contractions to norepinephrine by 2.0-fold in PARP-1(-/-) mice, and those to acetylcholine by 3.3-fold, respectively, as compared to PARP-1(+/+) mice. PEG-superoxide dismutase (SOD) and PEG-catalase prevented the effect of PQ on endothelium-dependent relaxations to acetylcholine in PARP-1(-/-) mice (p<0.001 vs. PQ treated PARP-1(+/+) mice. Indomethacin restored endothelium-dependent relaxations to acetylcholine in PQ treated PARP-1(-/-) mice (p<0.05 vs. PQ treated PARP-1(+/+).
  
  
  CONCLUSIONS
  PARP-1 protects from acute intracellular oxidative stress induced endothelial dysfunction by inhibiting ROS induced production of vasoconstrictor prostanoids.
authors: Cardiovascular Research, Physiology Institute, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors: Cathérine
authors: C
authors: Gebhard
authors: Barbara E
authors: BE
authors: Stähli
authors: Yi
authors: Y
authors: Shi
authors: Giovanni G
authors: GG
authors: Camici
authors: Alexander
authors: A
authors: Akhmedov
authors: Lisa
authors: L
authors: Hoegger
authors: Christine
authors: C
authors: Lohmann
authors: Christian M
authors: CM
authors: Matter
authors: Paul O
authors: PO
authors: Hassa
authors: Michael O
authors: MO
authors: Hottiger
authors: Tadeusz
authors: T
authors: Malinski
authors: Thomas F
authors: TF
authors: Lüscher
authors: Felix C
authors: FC
authors: Tanner
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D010269:Paraquat / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D014661:Vasoconstriction / Q000235:genetics / Q000502:physiology*; D014664:Vasodilation / Q000235:genetics / Q000502:physiology*
chemical_list: D011453:Prostaglandins; D017382:Reactive Oxygen Species; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D010269:Paraquat