Nitrosative stress and pharmacological modulation of heart failure

Pal Pacher, Richard Schulz, Lucas Liaudet, Csaba Szabó

    Research output: Contribution to journalReview article

    188 Scopus citations

    Abstract

    Dysregulation of nitric oxide (NO) and increased oxidative and nitrosative stress are implicated in the pathogenesis of heart failure. Peroxynitrite is a reactive oxidant that is produced from the reaction of nitric oxide with superoxide anion and impairs cardiovascular function through multiple mechanisms, including activation of matrix metalloproteinases (MMPs) and nuclear enzyme poly(ADP-ribose) polymerase (PARP). Recent studies suggest that the neutralization of peroxynitrite or pharmacological inhibition of MMPs and PARP are promising new approaches in the experimental therapy of various forms of myocardial injury. In this article, the role of nitrosative stress and downstream mechanisms, including activation of MMPs and PARP, in various forms of heart failure are discussed and novel emerging therapeutic strategies offered by neutralization of peroxynitrite and inhibition of MMPs and PARP in these pathophysiological conditions are reviewed.

    Original languageEnglish (US)
    Pages (from-to)302-310
    Number of pages9
    JournalTrends in Pharmacological Sciences
    Volume26
    Issue number6
    DOIs
    StatePublished - Jun 1 2005

    ASJC Scopus subject areas

    • Toxicology
    • Pharmacology

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