Antiasthma drug, ibudilast, inhibits neurogenic plasma extravasation in guinea-pig airways.
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 micrograms/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 micrograms/kg. Plasma extravasation induced by exogenous substance P (1 microgram/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.
Ichinose
M
M
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Kimura
K
K
Takahashi
T
T
Miura
M
M
Inoue
H
H
Takishima
T
T
Shirato
K
K
D000818:Animals; D001980:Bronchi / Q000098:blood supply / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000378:metabolism; D015633:Extravascular Lung Water / Q000187:drug effects* / Q000378:metabolism; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology; D006168:Guinea Pigs; D007275:Injections, Intravenous; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010949:Plasma / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D014132:Trachea / Q000098:blood supply / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology; D014867:Water; D007212:Indolizines; D011720:Pyrazoles
D001993:Bronchodilator Agents; D005070:Evans Blue; D005905:Glyburide; D011725:Pyridines; D014867:Water; C038366:ibudilast; D007212:Indolizines; D011720:Pyrazoles