A new, potent poly(ADP-ribose) polymerase inhibitor improves cardiac and vascular dysfunction associated with advanced aging

Pál Pacher, Anne Vaslin, Rita Benko, Jon G. Mabley, Lucas Liaudet, György Haskó, Anita Marton, Sándor Bátkai, Márk Kollai, Csaba Szabo

Research output: Contribution to journalArticle

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Abstract

Increased production of reactive oxygen and nitrogen species has recently been implicated in the pathogenesis of cardiac and 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, circulatory shock, and aging. Here, we investigated the effect of a new PARP inhibitor, INO-1001, on cardiac and endothelial dysfunction associated with advanced aging using Millar's new Aria pressure-volume conductance system and isolated aortic rings. Young adult (3 months old) and aging (24 months old) Fischer rats were treated for 2 months with vehicle, or the potent PARP inhibitor INO-1001. In the vehicle-treated aging animals, there was a marked reduction of both systolic and diastolic cardiac function and loss of endothelial relaxant responsiveness of aortic rings to acetylcholine. Treatment with INO-1001 improved cardiac performance in aging animals and also acetylcholine-induced, nitric oxide-mediated vascular relaxation. Thus, pharmacological inhibition of PARP may represent a novel approach to improve cardiac and vascular dysfunction associated with aging.

Original languageEnglish (US)
Pages (from-to)485-491
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume311
Issue number2
DOIs
StatePublished - Nov 2004
Externally publishedYes

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Blood Vessels
Poly(ADP-ribose) Polymerases
Acetylcholine
Reactive Nitrogen Species
Enzyme Activation
Inbred F344 Rats
Reperfusion Injury
Oxidants
Young Adult
Shock
Reactive Oxygen Species
Atherosclerosis
Nitric Oxide
Pharmacology
Hypertension
Pressure
Wounds and Injuries
INO 1001
Poly(ADP-ribose) Polymerase Inhibitors
Therapeutics

ASJC Scopus subject areas

  • Pharmacology

Cite this

A new, potent poly(ADP-ribose) polymerase inhibitor improves cardiac and vascular dysfunction associated with advanced aging. / Pacher, Pál; Vaslin, Anne; Benko, Rita; Mabley, Jon G.; Liaudet, Lucas; Haskó, György; Marton, Anita; Bátkai, Sándor; Kollai, Márk; Szabo, Csaba.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 311, No. 2, 11.2004, p. 485-491.

Research output: Contribution to journalArticle

Pacher, Pál ; Vaslin, Anne ; Benko, Rita ; Mabley, Jon G. ; Liaudet, Lucas ; Haskó, György ; Marton, Anita ; Bátkai, Sándor ; Kollai, Márk ; Szabo, Csaba. / A new, potent poly(ADP-ribose) polymerase inhibitor improves cardiac and vascular dysfunction associated with advanced aging. In: Journal of Pharmacology and Experimental Therapeutics. 2004 ; Vol. 311, No. 2. pp. 485-491.
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