Antiasthma drug, ibudilast, inhibits neurogenic plasma extravasation in guinea-pig airways

M. Ichinose, K. Kimura, T. Takahashi, M. Miura, H. Inoue, T. Takishima, K. Shirato

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6 Citations (Scopus)


We examined the effect of ibudilast, an antiasthma drug, on neurogenic microvascular leakage in guinea-pig airways by measuring extravasation of Evans blue dye. After intravenous pretreatment with atropine (1 mg/kg) and propranolol (1 mg/kg), bilateral vagal stimulation significantly increased nonadrenergic noncholinergic (NANC)-mediated leakage of dye in the trachea (Tr), the main bronchi (MB), and the central (cIPA) and peripheral (pIPA) intrapulmonary airways. Ibudilast (1.0 to 100 μg/kg given intravenously) did not affect basal leakage, but it significantly inhibited NANC-mediated plasma extravasation in a dose-dependent manner, with a maximal inhibition of 74.0% (Tr, p < 0.05), 89.1% (MB, p < 0.05), 91.4% (cIPA, p < 0.01), and 84.3% (pIPA, p < 0.05) at 100 μg/kg. Plasma extravasation induced by exogenous substance P (1 μg/kg given intravenously) was not inhibited by ibudilast. Glibenclamide, an inhibitor of ATP-sensitive potassium channels, blocked the inhibitory effect of ibudilast. We conclude that ibudilast inhibits neurogenic leakage by prejunctional inhibition of neuropeptide release from airway sensory nerve terminals via an ATP-sensitive potassium channel.

Original languageEnglish
Pages (from-to)431-434
Number of pages4
JournalAmerican Review of Respiratory Disease
Issue number2
Publication statusPublished - 1993

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine


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