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

  • Bedriniam Yilmaz Akdeniz University, Medical Faculty, Department of Pharmacology, 07070, Antalya, Turkey
  • Pinar Sahin Akdeniz University, Medical Faculty, Department of Histology and Embryology, 07070, Antalya, Turkey
  • Ece Ordueri Akdeniz University, Medical Faculty, Department of Histology and Embryology, 07070, Antalya, Turkey
  • Ciler Celik-Ozenci Akdeniz University, Medical Faculty, Department of Histology and Embryology, 07070, Antalya, Turkey
  • Arda Tasatargil Akdeniz University, Medical Faculty, Department of Pharmacology, 07070, Antalya, Turkey
Keywords: Endothelial dysfunction, endothelin-1, poly(ADP-ribose) polymerase (PARP)

Abstract

Aim. 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.

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Published
2014-06-16
How to Cite
Yilmaz, B., Sahin, P., Ordueri, E., Celik-Ozenci, C., & Tasatargil, A. (2014). Poly(ADP-ribose) polymerase inhibition improves endothelin-1-induced endothelial dysfunction in rat thoracic aorta. Upsala Journal of Medical Sciences, 119(3), 215–222. https://doi.org/10.3109/03009734.2014.908253
Section
Original Articles