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 Szabó

    Research output: Contribution to journalArticle

    76 Scopus citations

    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

    ASJC Scopus subject areas

    • Molecular Medicine
    • Pharmacology

    Fingerprint Dive into the research topics of 'A new, potent poly(ADP-ribose) polymerase inhibitor improves cardiac and vascular dysfunction associated with advanced aging'. Together they form a unique fingerprint.

  • Cite this

    Pacher, P., Vaslin, A., Benko, R., Mabley, J. G., Liaudet, L., Haskó, G., Marton, A., Bátkai, S., Kollai, M., & Szabó, C. (2004). A new, potent poly(ADP-ribose) polymerase inhibitor improves cardiac and vascular dysfunction associated with advanced aging. Journal of Pharmacology and Experimental Therapeutics, 311(2), 485-491. https://doi.org/10.1124/jpet.104.069658