Mercaptoethylguanidine, an inhibitor of nitric oxide synthase, and a scavenger of peroxynitrite exerts beneficial effects in hemorrhagic shock

B. Zingarelli, H. Ischiropoulos, A. L. Salzman, C. Szabó

    Research output: Contribution to journalArticle

    2 Scopus citations

    Abstract

    Part of the nitric oxide (NO) related cytotoxicity is mediated by peroxynitrite, a toxic oxidant species produced from NO and superoxide. We have recently observed that mercaptoethylguanidine (MEG) is an antiinflammatory agent with a combined mechanism of action. Its in vitro pharmacological effects include inhibition of the inducible isoform of nitric oxide synthase and scavenging peroxynitrite. Here we investigated the effect of MEG on the vascular decompensation and cellular energetic failure in a rat model of hemorrhagic shock (HS). HS was induced by rapid bleeding of the animals to 50 mmHg. At 3h animals were resuscitated with Ringers'-Lactate (the volume of shed blood, 9.2±0.7 ml) and monitored for subsequent 3h. In one group, MEG was administered at 10 mg/kg i.v. bolus, and 10 mg/kg/h infusion, starting from the resuscitation. MEG prevented the increase in plasma nitrite/nitrate and 6-keto-prostagIandin F1α levels associated with HS, ameliorated the fall in mean arterial blood pressure, and inhibited the development of vascular hyporeactivity of the thoracic aorta ex vivo. HS induced an increase in tyrosine nitration (a marker of peroxynitrite production) in the thoracic aortae ex vivo, which was abolished by MEG treatment. MEG ameliorated the decrease in the intracellular NAD+ content, the suppression of mitochondrial respiration and the development of DNA single strand breaks in peritoneal macrophages obtained from animals subjected to HS. Thus, MEG has protective effects in HS. The effects of MEG are likely to be related to a combined mode of action: selective inhibition of iNOS and scavenging of peroxynitrite.

    Original languageEnglish (US)
    Pages (from-to)A68
    JournalFASEB Journal
    Volume11
    Issue number3
    StatePublished - Dec 1 1997

    ASJC Scopus subject areas

    • Biotechnology
    • Biochemistry
    • Molecular Biology
    • Genetics

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