Inhibition of antigen-induced bronchial smooth muscle hyperresponsiveness by lovastatin in mice.
Statins have been proposed as a novel treatment of respiratory diseases. To determine the beneficial effects of statins on the airway hyperresponsiveness, a characteristic feature of allergic bronchial asthma, the effect of systemic treatment with lovastatin on antigen-induced bronchial smooth muscle hyperresponsiveness was investigated in mice. Male BALB/c mice were sensitized and repeatedly challenged with ovalbumin antigen. Animals were also treated with lovastatin (4 mg/kg/day, i.p.) once a day prior to and during the antigen inhalation period. The bronchial smooth muscle responsiveness to acetylcholine, but not to high K(+)-depolarization, was markedly and significantly augmented in the repeatedly antigen challenged mice. The bronchial smooth muscle hyperresponsiveness to acetylcholine induced by antigen exposure was significantly attenuated by the systemic treatment with lovastatin. Thus, lovastatin might have therapeutic potential to ameliorate airway hyperresponsiveness in allergic bronchial asthma.
Chiba
Yoshihiko
Y
Department of Pharmacology, School of Pharmacy, Hoshi University, Shinagawa-ku, Tokyo, Japan. chiba@hoshi.ac.jp
Sato
Shunsuke
S
Misawa
Miwa
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000009:adverse effects; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology*; D001285:Atropine / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology*; D001993:Bronchodilator Agents / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008148:Lovastatin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D010047:Ovalbumin / Q000008:administration & dosage / Q000009:adverse effects
D000941:Antigens; D001993:Bronchodilator Agents; D018678:Cholinergic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D001285:Atropine; D010047:Ovalbumin; D008148:Lovastatin; D000109:Acetylcholine; D007213:Indomethacin