Protective effects of nicotinamide against nitric oxide-mediated delayed vascular failure in endotoxic shock: Potential involvement of polyADP ribosyl synthetase

Basilia Zingarelli, Andrew L. Salzman, Csaba Szabó

    Research output: Contribution to journalArticle

    59 Scopus citations

    Abstract

    Nitric oxide (NO) produced by the inducible isoform of nitric oxide synthase contributes to the hypotension and vascular hyporeactivity in shock. Nicotinamide is protective against the cytotoxic effects of exogenous and endogenous NO in vitro. We investigated the effect of nicotinamide on the cellular energetic and vascular failure in a rat model of endotoxin shock. Administration of nicotinamide to rats, starting at 1 h after bacterial lipopolysaccharide, maintained higher blood pressure levels, without affecting induction of nitric oxide synthase. Nicotinamide treatment prevented the lipopolysaccharide-induced decrease in mitochondrial respiration and intracellular NAD+ levels in peritoneal macrophages and improved the contractility of the thoracic aorta ex vivo. Thus, nicotinamide protects against the delayed, NO-mediated vascular failure in endotoxic shock. Its actions are unrelated to inhibition of NO biosynthesis but may be related to inhibition of the NO-mediated activation of an energy-consuming DNA repair cycle triggered by polyADP ribose synthetase.

    Original languageEnglish (US)
    Pages (from-to)258-264
    Number of pages7
    JournalShock
    Volume5
    Issue number4
    DOIs
    StatePublished - Apr 1996

    ASJC Scopus subject areas

    • Emergency Medicine
    • Critical Care and Intensive Care Medicine

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