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Ups J Med Sci. 2014 Aug;119(3):215-22. doi: 10.3109/03009734.2014.908253. Epub 2014 Jun 16.

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

Author information

  • 1Akdeniz University, Medical Faculty, Department of Pharmacology , 07070, Antalya , Turkey.

Abstract

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 ┬Ámol/L) or PJ34 (an inhibitor of polyADP-ribose polymerase, 3 ┬Ámol/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.

KEYWORDS:

Endothelial dysfunction; endothelin-1; poly(ADP-ribose) polymerase (PARP)

PMID:
24932781
[PubMed - in process]
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