Allergic airway hyperresponsiveness and eosinophil infiltration is reduced by a selective iNOS inhibitor, 1400W, in mice

Akira Koarai, Masakazu Ichinose, Hisatoshi Sugiura, Shunsuke Yamagata, Toshio Hattori, Kunio Shirato

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Nitric oxide (NO) hyperproduction has been reported in asthmatic airways and may contribute to airway inflammatory responses. The purpose of this study was to examine the role of NO via inducible NO synthase (iNOS) in allergic airway inflammation using a selective iNOS inhibitor, N-[3-(aminomethyl)benzyl] acetamidine (1400W), in ovalbumin (OVA)-sensitized Balb/c mice. Sensitized animals were challenged with aerosolized 0.5% OVA for 1 h on two occasions 4 h apart. 1400W or the vehicle was administered by osmotic mini-pump from 2 h before to 24 h after OVA challenge. Twenty-four hours after OVA challenge, the vehicle-treated mice showed a significant airway hyperresponsiveness to intravenous methacholine (P<0.05) as well as an influx of eosinophils into the airways (P<0.05). iNOS immunoreactivity was obvious in the epithelial and, to a lesser extent, the infiltrated inflammatory cells. iNOS protein in the airway assessed by Western blotting also increased. Pretreatment with 1400W almost completely abolished the OVA-induced airway hyperresponsiveness and to a lesser extent eosinophil accumulation into the airways. These results suggest that NO synthesized by iNOS may participate in airway hyperresponsiveness and eosinophil infiltration into the airways after allergic reaction. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)267-275
Number of pages9
JournalPulmonary Pharmacology and Therapeutics
Volume13
Issue number6
DOIs
Publication statusPublished - 2000 Jan 1

Keywords

  • Airway resposiveness
  • Asthma
  • Eosinophil infiltration
  • Nitric oxide
  • iNOS immunoreactivity
  • iNOS protein

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Biochemistry, medical
  • Pharmacology (medical)

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