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Effect of cigarette smoke exposure in vivo on bronchial smooth muscle contractility in vitro in rats

Effect of cigarette smoke exposure in vivo on bronchial smoo...

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第十五届国际药理学大会

作者： norihide matsuuchi Yoshihiko Chiba Masahiko Murata Kroko Ushikubo Yuji Yoshikawa Akiyoshi Saitoh Hirovasu Sakai Junzo Kamei Miwa Msawa Dept of PharmacolSch of Pharmacy Hoshi Univ. 2-4-41 Ebara Shinagawa - ku Tokyo 142 -8501 JAPAN Dept of PharmacolSch of Pharmacy Hoshi Univ. 2-4-41 Ebara Shinagawa - ku Tokyo 142 -8501 JAPAN Dept of PharmacolSch of Pharmacy Hoshi Univ. 2-4-41 Ebara Shinagawa - ku Tokyo 142 -8501 JAPAN Dept of PharmacolSch of Pharmacy Hoshi Univ. 2-4-41 Ebara Shinagawa - ku Tokyo 142 -8501 JAPAN Dept of Pathophysiol and Therap.Sch of Pharmacy Hoshi Univ. 2-4-41 Ebara Shinagawa - ku Tokyo 142 -8501 JAPAN Dept of Pathophysiol and Therap.Sch of Pharmacy Hoshi Univ. 2-4-41 Ebara Shinagawa - ku Tokyo 142 -8501 JAPAN Dept of PharmacolSch of Pharmacy Hoshi Univ. 2-4-41 Ebara Shinagawa - ku Tokyo 142 -8501 JAPAN Dept of Pathophysiol and Therap.Sch of Pharmacy Hoshi Univ 2-4-41 Ebara Shinagawa - ku Tokyo 142 -8501 JAPAN Dept of PharmacolSch of Pharmacy Hoshi Univ. 2-4-41 Ebara Shinagawa - ku Tokyo 142 -8501 JAPAN

＜正＞ Cigarette smoking is a risk factor for the development of chronic obstructive pulmonary disease （COPD） and airway hyperresponsiveness. The effect of cigarette smoking on the contractility of airway smooth muscle is however unclear. The present study was performed to determine the responsiveness of bronchial smooth muscle （BSM） isolated from rats that were exposed （for 2 h/d. every day. 2 wk） to mainstream cigarette smoke in vivo. The responsiveness of intact BSM isolated from cigarette smoke- exposed rats to ACh. but not to high K+ - depolarization, was significantly augmented when compared with that from air - exposed control group. In permeabilized BSM strips, the ACh- induced Ca2 + sen-sitization of contraction was significantly augmented in rats exposed to cigarette smoke, although the contraction induced by Ca2 + was within control level. Immunoblotanalyses revealed an increased expression of RhoA protein in the BSM 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.

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