METOPROLOL DOES NOT ATTENUATE ATHEROSCLEROSIS IN LIPID-FED RABBITS EXPOSED TO ENVIRONMENTAL TOBACCO-SMOKE

Background We previously demonstrated that exposure to environmental t obacco smoke (ETS) increases the development of atherosclerosis in lip id-fed rabbits. Clinical studies have suggested a protective effect of beta-blockers in smokers. Accordingly, we evaluated the effects of me toprolol in this animal model to see whether this beta-blocker would b lock the atherogenic effects of ETS. Methods and Results Thirty-two Ne w 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(-1).h(-1) administered subcutaneously by an osmotic pump. Rabb its in the ETS groups were exposed to sidestream smoke from four Marlb oro cigarettes per 15 minutes, 6 hours a day, for 10 weeks. Average ai r carbon monoxide (CO), nicotine, and total particulates (TP) in the e xposure chambers were 67.2+/-3.1 (SEM) ppm, 1133.7+/-78.4 mu g/m(3), a nd 37.7+/-3.0 mg/m(3), respectively. Plasma nicotine was significantly higher in ETS-exposed rabbits than in nonexposed rabbits (7.1+/-1.9 v ersus 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 g roup (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 meteprolol-treated rabbits (51+/-1% versus 38+/-1%, P =.027). The benefit of metoprolol was independent of ETS exposure (ETS x metoprolol interaction, P=.595). Conclusions Exposure to ETS signif icantly accelerated and metoprolol decreased the development of athero sclerosis in lipid-fed rabbits, but there was no interaction between t he effects of ETS exposure and metoprolol. Metoprolol did not protect against the effects of ETS on atherosclerosis, suggesting that the bet a-adrenergic system is not the mechanism of ETS-induced atherosclerosi s.