Published ahead of print on September 15, 2005, doi:10.1165/rcmb.2005-0177OC Am. J. Respir. Cell Mol. Biol., Volume 33, Number 6, December 2005, 574-581 A more recent version of this article appeared on December 1, 2005
Submitted on May 10, 2005 Effect of Cigarette Smoke Exposure In Vivo on Bronchial Smooth Muscle Contractility In Vitro in RatsYoshihiko Chiba1*,1 Department of Pharmacology, Hoshi University, School of Pharmacy, Tokyo, Japan, 2 Department of Pathophysiology and Therapeutics, Hoshi University, School of Pharmacy, Tokyo, Japan * To whom correspondence should be addressed. E-mail: chiba{at}hoshi.ac.jp.
Cigarette smoking is a risk factor for development of airway hyperresponsiveness and chronic obstructive pulmonary disease (COPD). However, little is known concerning the effect of cigarette smoking on the contractility of airway smooth muscle. The current study was carried out to determine the responsiveness of bronchial smooth muscles isolated from the rats that were subacutely exposed to mainstream cigarette smoke in vivo. Male Wistar rats were exposed to diluted mainstream cigarette smoke for 2 hours/day, everyday for 2 weeks. 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 (BAL) fluids and peribronchial tissues, was observed. In these subacutely cigarette smoke-exposed animals, the responsiveness of isolated intact (non-permeabilized) bronchial smooth muscle to acetylcholine (ACh), but not to high K+-depolarization, was significantly augmented when compared with air-exposed control group. In
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-toxin-permeabilized bronchial smooth muscle strips, the ACh-induced Ca2+ sensitization of contraction was significantly augmented in the cigarette smoke-exposed rats although the contraction induced by Ca2+ itself 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 would have relevance to airway hyperresponsiveness in patients with COPD.
