Airway hyperresponsiveness in cigarette smoke-exposed rats.
To investigate the possibility that altered airway-parenchymal interaction may account for bronchial hyperresponsiveness induced by cigarette smoke exposure, we tested the effect of administration of cigarette smoke (SM), elastase (EL), and both SM and EL on airway responsiveness in 41 Long-Evans male rats. Twelve were exposed to 30 puffs of SM for 15 weeks; 8 received a single intratracheal injection of EL (250 IU/kg); 9 received both EL and SM exposure (SE); 12 control rats were exposed to room air (CO). After 15 weeks, animals were anesthetized and mechanically ventilated (Vt = 2.5 ml, f = 80/min). Methacholine (MCh) dose-response curves (DRCs) were constructed by calculating pulmonary resistance (RL) after ultrasonic nebulization of saline followed by doubling concentrations of MCh (0.0625-256 mg/ml). Exposure to cigarette smoking, with or without elastase, led to a significant reduction in body weight and increased total lung capacity (TLC) compared to exposure to CO. However, there was no significant change in static compliance in the experimental groups, despite increased lung volume. The concentration resulting in a doubling of RL (EC200RL) was significantly lower in rats treated with SM (n = 7) than CO (n = 8) (3.3 vs. 56.1 mg/ml, geometric mean, p < 0.01). The concentration at which a maximal RL was achieved was lower in SM than CO, EL, and SE (p < 0.05). To assess the possible influence of airway-parenchymal interaction on responsiveness, we measured RL both at functional residual capacity (FRC) and at a volume above FRC equivalent to 1 tidal volume. RL changed similarly in all groups. Despite similar effects on mechanics of both cigarette smoke exposure and elastase administration, only cigarette smoke-exposed animals exhibited evidence of hyperresponsiveness. In this model cigarette smoke-induced hyperresponsiveness is unrelated to changes in either lung elasticity or airway-parenchymal interaction.
Xu
L J
LJ
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Dandurand
R J
RJ
Lei
M
M
Eidelman
D H
DH
D000403:Airway Resistance / Q000502:physiology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D004305:Dose-Response Relationship, Drug; D005652:Functional Residual Capacity / Q000502:physiology; D008170:Lung Compliance / Q000502:physiology; D008297:Male; D016210:Methacholine Chloride; D010196:Pancreatic Elastase / Q000502:physiology; D051381:Rats; D012907:Smoking / Q000503:physiopathology*; D014109:Total Lung Capacity / Q000502:physiology
D016210:Methacholine Chloride; D010196:Pancreatic Elastase