Effect of cigarette smoke exposure in vivo on bronchial smooth muscle contractility in vitro in rats.
Cigarette smoking is a risk factor for the development of airway hyperresponsiveness and chronic obstructive pulmonary disease. Little is known concerning the effect of cigarette smoking on the contractility of airway smooth muscle. The current study was performed to determine the responsiveness of bronchial smooth muscles isolated from rats that were subacutely exposed to mainstream cigarette smoke in vivo. Male Wistar rats were exposed to diluted mainstream cigarette smoke for 2 h/d every day for 2 wk. Twenty-four hours after the last cigarette smoke exposure, a marked airway inflammation (i.e., increases in numbers of neutrophils, lymphocytes, and macrophages in bronchoalveolar lavage fluid and peribronchial tissues) was observed. In these subacutely cigarette smoke-exposed animals, the responsiveness of isolated intact (nonpermeabilized) bronchial smooth muscle to acetylcholine, but not to high K+ -depolarization, was significantly augmented when compared with the air-exposed control group. In alpha-toxin-permeabilized bronchial smooth muscle strips, the acetylcholine-induced Ca2+ sensitization of contraction was significantly augmented in rats exposed to cigarette smoke, although the contraction induced by Ca2+ was control level. Immunoblot analyses revealed an increased expression of RhoA protein in the bronchial smooth muscle of rats that were exposed to cigarette smoke. Taken together, these findings suggest that the augmented agonist-induced, RhoA-mediated Ca2+ sensitization may be responsible for the enhanced bronchial smooth muscle contraction induced by cigarette smoking, which has relevance to airway hyperresponsiveness in patients with chronic obstructive pulmonary disease.
Chiba
Yoshihiko
Y
Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. chiba@hoshi.ac.jp
Murata
Masahiko
M
Ushikubo
Hiroko
H
Yoshikawa
Yuji
Y
Saitoh
Akiyoshi
A
Sakai
Hiroyasu
H
Kamei
Junzo
J
Misawa
Miwa
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D015151:Immunoblotting; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012907:Smoking; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D010738:Type C Phospholipases / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D014028:Tobacco Smoke Pollution; D014665:Vasodilator Agents; D010738:Type C Phospholipases; D020742:rhoA GTP-Binding Protein; D000109:Acetylcholine; D002118:Calcium