Augmentation of elastase-induced emphysema by cigarette smoke. Effects of reduced nicotine content.
To examine the role of nicotine in the augmentation of elastase-induced emphysema by cigarette smoke, animals that had been pretreated with porcine pancreatic elastase (PPE) were exposed to cigarette smokes that had a five-fold difference in their nicotine concentrations. Young adult female Long-Evans rats were divided into seven groups: (1) untreated controls; (2) low nicotine cigarette smoke exposure (Kentucky 2A1 reference cigarettes; 35.0 mg total particulate matter, 0.42 mg nicotine, and 0.38 mg nitrogen oxides per cigarette); (3) high nicotine cigarette smoke exposure (Kentucky 2R1 reference cigarettes; 38.8 mg total particulate matter, 2.2 mg nicotine, and 0.34 mg nitrogen oxides per cigarette; (4) PPE alone; (5) PPE + sham smoke exposure; (6) PPE + 2A1 smoke exposure; and (7) PPE + 2R1 smoke exposure. Three days after intratracheal administration of PPE (400 IU/kg), animals in the smoke-treated groups were exposed to 10 puffs of cigarette smoke daily, 7 days/wk for 14 wk. Sham-treated animals received room air in place of cigarette smoke. After the exposures, pulmonary function tests were performed under general anesthesia. Whole lungs were examined for gross pathologic changes, and samples of lung tissue were harvested for quantitative morphometry. Cigarette smoke exposure alone did not produce significant changes in pulmonary function or structure. On the other hand, treatment with elastase alone produced a constellation of pulmonary functional and structural changes that were pathognomonic of emphysema. Exposure to 2R1 but not 2A1 cigarette smoke significantly augmented the emphysematous changes produced by PPE.(ABSTRACT TRUNCATED AT 250 WORDS)
Diamond
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Pharmacology and Toxicology Division, University of Kentucky, College of Pharmacy, Lexington.
Kimmel
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EC
Lai
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Winsett
D W
DW
D000818:Animals; D005260:Female; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D009538:Nicotine / Q000009:adverse effects* / Q000494:pharmacology; D010196:Pancreatic Elastase / Q000494:pharmacology; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D012907:Smoking / Q000009:adverse effects*
D009538:Nicotine; D010196:Pancreatic Elastase