title: Metoprolol does not attenuate atherosclerosis in lipid-fed rabbits exposed to environmental tobacco smoke.
abstract: 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 beta-blockers in smokers. Accordingly, we evaluated the effects of metoprolol in this animal model to see whether this beta-blocker would block the atherogenic effects of ETS.
  
  
  RESULTS
  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-1.h-1 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 micrograms/m3, and 37.7 +/- 3.0 mg/m3, 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 (ETS x metoprolol interaction, P = .595).
  
  
  CONCLUSIONS
  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 beta-adrenergic system is not the mechanism of ETS-induced atherosclerosis.
authors.affiliation: Department of Medicine, University of California, San Francisco 94143-0124.
authors.forename: Y P
authors.initials: YP
authors.lastname: Sun
authors.forename: B Q
authors.initials: BQ
authors.lastname: Zhu
authors.forename: R E
authors.initials: RE
authors.lastname: Sievers
authors.forename: S A
authors.initials: SA
authors.lastname: Glantz
authors.forename: W W
authors.initials: WW
authors.lastname: Parmley
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D011651:Pulmonary Artery / Q000473:pathology; D011817:Rabbits; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D002791:Cholesterol, Dietary; D014028:Tobacco Smoke Pollution; D008790:Metoprolol