Poly(ADP-ribose) polymerase inhibition improves endothelin-1-induced endothelial dysfunction in rat thoracic aorta

• Published in: Upsala journal of medical sciences 2014-08, Vol.119 (3), p.215-222
• Main Authors: Yilmaz, Bedriniam, Sahin, Pinar, Ordueri, Ece, Celik-Ozenci, Ciler, Tasatargil, Arda
• Format: Article
• Language: English
• Subjects: Animals; Aorta, Thoracic - enzymology; Aorta, Thoracic - metabolism; Aorta, Thoracic - physiopathology; Coronary vessels; Endothelial dysfunction; endothelin-1; Endothelin-1 - physiology; Endothelium; Endothelium, Vascular - enzymology; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiopathology; Male; Nitric oxide; Original; poly(ADP-ribose) polymerase (PARP); Poly(ADP-ribose) Polymerase Inhibitors; Polyethylene glycol; Polyethylene Glycols - administration & dosage; Rats; Rats, Wistar; Superoxide Dismutase - administration & dosage
• ISSN: 0300-9734; 2000-1967
• DOI: 10.3109/03009734.2014.908253

AbstractAim. 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.Conclusion. 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.