Endothelial dysfunction in aging animals: The role of poly(ADP-ribose) polymerase activation

Pál Pacher, Jon G. Mabley, Francisco G. Soriano, Lucas Liaudet, Katalin Komjáti, Csaba Szabó

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78 Citations (Scopus)

Abstract

Recent work has demonstrated the production of reactive oxygen and nitrogen species in the vasculature of aging animals. Oxidant induced cell injury triggers the activation of nuclear enzyme poly(ADP ribose) polymerase (PARP) leading to endothelial dysfunction in various pathophysiological conditions (reperfusion, shock, diabetes). Here we studied whether the loss of endothelial function in aging rats is dependent upon the PARP pathway within the vasculature. Young (3 months-old) and aging (22 months-old) Wistar rats were treated for 2 months with vehicle or the PARP inhibitor PJ34. In the vehicle-treated aging animals there was a significant loss of endothelial function, as measured by the relaxant responsiveness of vascular rings to acetylcholine. Treatment with PJ34, a potent PARP inhibitor, restored normal endothelial function. There was no impairment of the contractile function and endothelium-independent vasodilatation in aging rats. Furthermore, we found no deterioration in the myocardial contractile function in aging animals. Thus, intraendothelial PARP activation may contribute to endothelial dysfunction associated with aging.

Original languageEnglish
Pages (from-to)1347-1350
Number of pages4
JournalBritish journal of pharmacology
Volume135
Issue number6
DOIs
Publication statusPublished - Jan 1 2002

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Keywords

  • Aging
  • Cardiac function
  • Endothelial dysfunction
  • Poly(ADP ribose) polymerase

ASJC Scopus subject areas

  • Pharmacology

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