Peroxynitrite induces airway hyperresponsiveness in guinea pigs in vitro and in vivo

Gudarz Sadeghi-Hashjin, Gert Folkerts, Paul A. J. Henricks, Alfons K. C. P. Verheyen, Henk J. Van Der Linde, Ingrid Van Ark, Astrid Coene, Frans P. Nijkamp

    Research output: Contribution to journalArticleAcademicpeer-review

    Abstract

    Peroxynitrite (ONOO-) is a cytotoxic product of the rapid reaction between nitric oxide and superoxide that may initiate inflammation. Isolated perfused tracheas from guinea pigs were incubated from the mucosal side for 15 min with peroxynitrite (1 to 100 μM). Thereafter, concentration-response curves to histamine and methacholine were constructed on the preparations. Peroxynitrite (10 μM) caused a significant hyperresponsiveness; the maximal contractions in response to histamine and methacholine were enhanced by 30% and 40%, respectively. In the peroxynitrite-treated group, clear epithelial damage as well as eosinophil destruction were detected. Moreover, 3, 5, and 10 days after intratracheal instillation of peroxynitrite (100 nmol), a significant rise in pulmonary resistance to histamine of anesthetized animals was observed. It is suggested that the generation of peroxynitrite from nitric oxide and superoxide radicals during inflammatory processes induces epithelial damage, mediator release, and hence airway hyperresponsiveness. These findings may have clinical implications, because airway inflammation, epithelial damage, and hyperresponsiveness are characteristic features in patients suffering from asthma.
    Original languageEnglish
    Pages (from-to)1697-1701
    Number of pages5
    JournalAmerican Journal of Respiratory and Critical Care Medicine
    Volume153
    Issue number5
    Publication statusPublished - 26 Jan 1996

    Keywords

    • histamine
    • methacholine
    • nitric oxide
    • nitrite
    • peroxynitrite
    • superoxide
    • animal tissue
    • article
    • bronchus hyperreactivity
    • cell damage
    • controlled study
    • guinea pig
    • lung resistance
    • male
    • nonhuman
    • priority journal
    • respiratory epithelium
    • trachea

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