Activation of poly(ADP-ribose) polymerase contributes to the endothelial dysfunction associated with hypertension and aging.

Pal Pacher, Jon G. Mabley, Francisco G. Soriano, Lucas Liaudet, Csaba Szabo

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Increased production of reactive oxygen and nitrogen species has recently been implicated in the pathogenesis of endothelial dysfunction associated with atherosclerosis, hypertension and aging. Oxidant induced cell injury triggers the activation of nuclear enzyme poly(ADP-ribose) polymerase (PARP), which in turn contributes to cardiac and vascular dysfunction in various pathophysiological conditions including diabetes, reperfusion injury and circulatory shock. Here we investigated the role of PARP activation in the pathogenesis of cardiac and endothelial dysfunction associated with atherosclerosis, hypertension and aging. Retired breeder spontaneously hypertensive rats (SHR, 40 weeks old) and apolipoprotein E knockout mice (apoE-Ko, 10 weeks old) were treated for 20 weeks with vehicle or the potent PARP inhibitor PJ34. In the vehicle-treated SHR rats and apoE-Ko mice (kept on atherogenic diet) there was a significant loss of endothelial function, as measured by the relaxant responsiveness of vascular rings to acetylcholine. SHR rats also developed severe hypertension and cardiac hypertrophy. Treatment with the PARP inhibitor did not influence high blood pressure and cardiac hypertrophy in SHR rats, but it improved Ach-induced, NO-mediated vascular relaxation. In addition to the beneficial effects of chronic treatment with PARP inhibitor, 1-h in vitro incubation of aortic rings from SHR rats with PJ34 (3 micromol/l) was also able to improve the endothelial dysfunction. In contrast, in apoE-Ko mice PJ34 treatment did not affect the parameters studied. Thus, PARP activation contributes to the pathogenesis of endothelial dysfunction associated with hypertension and aging, but not in the current experimental model of atherosclerosis.

Original languageEnglish (US)
Pages (from-to)659-664
Number of pages6
JournalInternational Journal of Molecular Medicine
Volume9
Issue number6
StatePublished - Jun 2002
Externally publishedYes

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Poly(ADP-ribose) Polymerases
Inbred SHR Rats
Apolipoproteins E
Hypertension
Blood Vessels
Atherosclerosis
Cardiomegaly
Atherogenic Diet
Reactive Nitrogen Species
Enzyme Activation
Reperfusion Injury
Oxidants
Knockout Mice
Acetylcholine
Shock
Reactive Oxygen Species
Theoretical Models
Wounds and Injuries
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride
Poly(ADP-ribose) Polymerase Inhibitors

ASJC Scopus subject areas

  • Genetics

Cite this

Activation of poly(ADP-ribose) polymerase contributes to the endothelial dysfunction associated with hypertension and aging. / Pacher, Pal; Mabley, Jon G.; Soriano, Francisco G.; Liaudet, Lucas; Szabo, Csaba.

In: International Journal of Molecular Medicine, Vol. 9, No. 6, 06.2002, p. 659-664.

Research output: Contribution to journalArticle

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