title: Poly(ADP-ribose) polymerase inhibition improves endothelin-1-induced endothelial dysfunction in rat thoracic aorta.
abstract: OBJECTIVE
  The aim of this study was to investigate whether poly(ADP-ribose) polymerase (PARP) inhibition improves endothelin-1 (ET-1)-induced endothelial dysfunction (ED).
  
  
  METHODS
  Isolated rat thoracic aorta rings were incubated with ET-1 (10 nmol/L) in the presence or absence of either polyethylene glycol-superoxide dismutase (PEG-SOD; a cell-permeable superoxide radical scavenger, 41 U/mL) plus apocynin (a NADPH oxidase inhibitor, 300 µmol/L) or PJ34 (an inhibitor of polyADP-ribose polymerase, 3 µmol/L) for 18 h. Isometric tension studies were performed in response to acetylcholine (ACh; an endothelium-dependent vasodilator), sodium nitroprusside (SNP; an endothelium-independent vasodilator), and phenylephrine (Phe). PARP-1 and PAR (an end-product of PARP activity) expressions were evaluated by both Western blot and immunohistochemistry.
  
  
  RESULTS
  Incubation of thoracic aorta rings with ET-1 resulted in a significant inhibition of the response to ACh, while SNP-induced relaxation was unaffected. The contractile response to Phe increased in arteries that were incubated with ET-1. PARP-1 and PAR expressions increased after ET-1 incubation. The diminished vasoreactivity as well as changes in expressions of PARP-1 and PAR in ET-1-incubated vessels were improved by both PEG-SOD plus apocynin and PJ34.
  
  
  CONCLUSIONS
  Our studies demonstrate that ED induced by ET-1 seems to be effected via oxidative stress in the thoracic aorta endothelium with subsequent activation of the PARP pathway.
authors.affiliation: Akdeniz University, Medical Faculty, Department of Pharmacology , 07070, Antalya , Turkey.
authors.forename: Bedriniam
authors.initials: B
authors.lastname: Yilmaz
authors.forename: Pinar
authors.initials: P
authors.lastname: Sahin
authors.forename: Ece
authors.initials: E
authors.lastname: Ordueri
authors.forename: Ciler
authors.initials: C
authors.lastname: Celik-Ozenci
authors.forename: Arda
authors.initials: A
authors.lastname: Tasatargil
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D019332:Endothelin-1 / Q000502:physiology*; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011092:Polyethylene Glycols / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000008:administration & dosage
chemical_list: D019332:Endothelin-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011092:Polyethylene Glycols; D013482:Superoxide Dismutase
keywords: Endothelial dysfunction; endothelin-1; poly(ADP-ribose) polymerase (PARP)