The role of nicotine in the pathogenesis of pulmonary emphysema.
An investigation was undertaken to evaluate the potential role of nicotine in the pathogenesis of pulmonary emphysema. The acute lethality and the pulmonary toxicity of a single endotracheally administered dose of nicotine were studied in Long-Evans rats. The 24-h LD50 of nicotine was established at 19.3 +/- SD 5.4 mg/kg. Subsequently, rats were treated with either nicotine alone (3 or 7.5 mg/kg), porcine pancreatic elastase (PPE) alone (200 IU/kg) or PPE (200 IU/kg) followed 5 days later by nicotine (3 mg/kg). The selected dose of PPE was below the threshold dose for induction of emphysematous lesions. Cage and sham-treated control groups also were included in the investigation. Four weeks after treatment, extensive physiologic tests were conducted to evaluate the ventilatory, mechanical, and gas exchange functions of the lungs. Lung tissue specimens also were taken for estimation of tissue volume density. Although a few isolated incidents of significant intergroup differences were observed, no distinctive pattern of functional or structural change reminiscent of emphysema was noted in any of the experimental groups. It is concluded that endotracheal instillation of a single, relatively high, dose of nicotine neither induces nor augments the development of pulmonary emphysema in the rat.
D000818:Animals; D002248:Carbon Monoxide / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D008168:Lung / Q000473:pathology; D008170:Lung Compliance; D008176:Lung Volume Measurements; D009538:Nicotine / Q000633:toxicity*; D010196:Pancreatic Elastase; D011656:Pulmonary Emphysema / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D011659:Pulmonary Gas Exchange; D051381:Rats
D009538:Nicotine; D002248:Carbon Monoxide; D010196:Pancreatic Elastase