title: Different effects of smoke from heavy and light cigarettes on the induction of bronchial smooth muscle hyperresponsiveness in rats.
abstract: Cigarette smoking is one of the main risk factors in the development of chronic obstructive pulmonary disease (COPD). It has been suggested that an augmented agonist-induced, RhoA mediated Ca²⁺ sensitization is responsible for the enhanced bronchial smooth muscle contraction induced by cigarette smoking. In the present study, to determine whether or not these phenomena are dependent on the degree of exposure to the components of cigarette smoke, we examined the effects of exposure to mainstream smoke derived from either light or heavy cigarettes on both the contractile responsiveness and the expression of RhoA in bronchial smooth muscle. Male Wistar rats were exposed to mainstream cigarette smoke for 2 hr/day for 2 weeks. Twenty-four hr after the last cigarette smoke exposure, we measured isometrical contractions of the bronchial smooth muscle. The concentration-response curve to ACh was significantly shifted upward after heavy cigarette smoke (HCS) exposure, whereas no significant difference was observed in the case of light cigarette smoke (LCS) exposure compared with control rats. No significant difference in K⁺ responsiveness was observed between the groups. The expression of RhoA protein in bronchial preparations from rats repeatedly exposed to HCS, but not to LCS, was significantly increased as compared with that of the control animals. On the other hand, inhalation of nicotine had no effect on either the ACh- and high K⁺ depolarization-induced contractions or the expression of RhoA protein. The increased expression of RhoA seems to have an important role in the augmented contractile responses of the airways in rats, a characteristic feature of early COPD.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan. sakai@hoshi.ac.jp
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Sakai
authors.forename: Akiko
authors.initials: A
authors.lastname: Fujita
authors.forename: Ayako
authors.initials: A
authors.lastname: Watanabe
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Chiba
authors.forename: Junzo
authors.initials: J
authors.lastname: Kamei
authors.forename: Miwa
authors.initials: M
authors.lastname: Misawa
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000502:physiology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking; D014026:Nicotiana; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis
chemical_list: D012906:Smoke; D009538:Nicotine; D020742:rhoA GTP-Binding Protein; D000109:Acetylcholine