Allergic airway hyperresponsiveness and eosinophil infiltration is reduced by a selective iNOS inhibitor, 1400W, in mice.
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.
Koarai
A
A
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Ichinose
M
M
Sugiura
H
H
Yamagata
S
S
Hattori
T
T
Shirato
K
K
D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology*; D015153:Blotting, Western; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004804:Eosinophils / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000737:chemistry* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D012137:Respiratory System / Q000276:immunology
D000578:Amidines; D001596:Benzylamines; D004791:Enzyme Inhibitors; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase