title: Aldosterone-induced endothelial dysfunction of rat aorta: role of poly(ADP-ribose) activation.
abstract: BACKGROUND
  The aim of this study was to investigate whether activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) contributes to the development of aldosterone-induced endothelial dysfunction and treatment with the potent PARP inhibitor 1,5-isoquinolinediol (3 mg/kg/day, i.p.) could prevent endothelial dysfunction caused by aldosterone.
  
  
  METHODS
  Infusion of subpressor doses of aldosterone with subcutaneously implanted mini-osmotic pumps (0.05 mg/kg/day) to rats for 21 days induced the development of endothelial dysfunction. In order to evaluate endothelial function, isometric tension studies were performed in response to acetylcholine and sodium nitroprusside.Additionally, PAR (the end product of activated PARP) and PARP-1 expressions in the endothelium of thoracic aortas were evaluated by immunohistochemistry.
  
  
  RESULTS
  There was a significant loss of endothelium-dependent vasodilatation in response to acetylcholine in aldosterone-infused rats. In animals treated with 1,5-isoquinolinediol, the effect of aldosterone on vascular responsiveness was less than the untreated groups. Immunohistochemical studies demonstrated that aldosterone administration increased PAR and PARP-1 expressions in the endothelium of thoracic aortas, whereas PARP inhibition decreased their expressions to control levels.
  
  
  CONCLUSIONS
  Our results indicate that PARP activation in the vascular system may be a contributory factor to the impaired endothelial function associated with aldosterone administration.
authors.affiliation: Department of Pharmacology, Medical Faculty, Akdeniz University, 07070 Antalya, Turkey. ardatas@akdeniz.edu.tr
authors.forename: Arda
authors.initials: A
authors.lastname: Tasatargil
authors.forename: Merih
authors.initials: M
authors.lastname: Tekcan
authors.forename: Ciler
authors.initials: C
authors.lastname: Celik-Ozenci
authors.forename: Nazli
authors.initials: N
authors.lastname: Ece Gungor
authors.forename: Bedriniam
authors.initials: B
authors.lastname: Dalkiran
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000450:Aldosterone / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*; D017209:Apoptosis / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010616:Phenanthrenes / Q000494:pharmacology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D010616:Phenanthrenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009599:Nitroprusside; D000450:Aldosterone; D011065:Poly(ADP-ribose) Polymerases; D007545:Isoproterenol; D000109:Acetylcholine