Quantitative analysis of antiatherosclerotic effect of nifedipine in cholesterol-fed rabbits

Abstract

Reports concerning the effect of slow calcium-channel blockers on experimental atherosclerosis are controversial. We examined the antiatherosclerotic effect of nifedipine (40 mg/day for 16 weeks) on aorta of rabbits on diets containing 0.3%, 0.5%, and 1.0% cholesterol. There were no significant differences in levels of serum lipids with or without nifedipine in the same cholesterol-fed rabbits. The results obtained show that nifedipine suppressed the extent of lipid deposition and surface involvement (S.I.) in aorta in 0.3% cholesterol-fed rabbits, whereas nifedipine only tended to suppress S.I. in 0.5% cholesterol-fed rabbits and had no effect in 1.0% cholesterol-fed rabbits. The log dose-response relationship of S.I. was obtained by plotting the concentration of cholesterol in the feed or the "integrated value" of the total serum cholesterol (TC), i.e., the cumulative sum of the serum TC values obtained at each week. The log dose-response curve was shifted in parallel with the right in nifedipine groups. The Lineweaver-Burk plot constructed from the dose-response curve had the same points crossing the ordinate with or without nifedipine. These results suggested that nifedipine suppressed S.I. in a competitive manner with cholesterol on the specific binding site of lipid deposition. Electron-microscopic findings also demonstrated that fat droplets in smooth muscle cells, extracellular matrix containing collagen, and elastic fibers decreased in nifedipine-treated rabbits.