Lipid-Fed Rabbits Exposed to Environmental Tobacco Smoke

Background We previously demonstrated that exposure to environmental tobacco smoke (ETS) increases the development of atherosclerosis in lipid-fed rabbits. Clinical studies have suggested a protective effect of 3-blockers in smokers. Accordingly, we evaluated the effects of metoprolol in this animal model to see whether this 3-blocker would block the atherogenic effects of ETS. Mehos and Rdsus Thirty-two New Zealand White male rabbits on a 0.3% cholesterol diet were randomly divided into four groups: ETS-metoprolol (ETS-M), ETS-control (ETS-C), and non-ETS with metoprolol (NETS-M) and without metoprolol (NETS-C). The two metoprolol-treated groups received metoprolol at a dose of 0.4 mg kg`. h1 administered subcutaneously by an osmotic pump. Rabbits in the ETS groups were exposed to sidestream smoke from four Marlboro cigarettes per 15 minutes, 6 hours a day, for 10 weeks. Average air carbon monoxide (CO), nicotine, and total particulates (TP) in the exposure chambers were 67.2±3.1 (SEM) ppm, 1133.7±78.4 jug/m3, and 37.7±3.0 mg/im, respectively. Plasma nicotine was significantly higher in ETS-exposed rabbits than in nonexposed rabbits (7.1±1.9 versus 0.5±0.1 ng/mL, P<.01). Blood carbon monoxide hemoglobin (COHb) in the ETS-M group was significantly higher than that in the NETS-M group (4.0±0.2% versus 1.3±0.1%, P<.0001). The lipid lesions in the aorta and pulmonary artery were 57.2±7.6% and 33.1±6.4% (ETS-M), 62.8±8.4% and 58.4±6.1% (ETS-C), 38.7±9.4% and 24.8±7.7% (NETS-M), and 49.8±8.7% and 32.7±7.1% (NETS-C). There were significant differences in lipid deposits of the arteries between the controls and the ETS-exposed rabbits (37±1% versus 53±1%, P=.004) and between the controls and metoprolol-treated rabbits (51±1% versus 38±1%, P=.027). The benefit of metoprolol was independent of ETS exposure (ETSxmetoprolol interaction, P=.595). Concluions Exposure to ETS significantly accelerated and metoprolol decreased the development of atherosclerosis in lipid-fed rabbits, but there was no interaction between the effects of ETS exposure and metoprolol. Metoprolol did not protect against the effects of ETS on atherosclerosis, suggesting that the /3-adrenergic system is not the mechanism of ETS-induced atherosclerosis. (Cirnuaion. 1994;89.2260-2265.)