No abstract

The objective of this study was to examine the suppressive effect of nifedipine on intramural coronary arterial lesions in cholesterol-fed rabbits. Each rabbit in Groups A (n=6) and B (n=5) was fed a 0.3% cholesterol diet and was orally administered nifedipine (40 mg/day) or placebo. Each rabbit in Groups C (n=5) and D (n=6) was fed a 0.5% cholesterol diet and was orally administered nifedipine (40 mg/day) or placebo. The serum concentrations of total cholesterol (TC) were determined at 1-week intervals to calculate the integrated values. The lesion induction ratio was defined as the ratio of intramural coronary arteries 50-150 microm in diameter with arterial lipoidosis to the total number of arteries of the same diameter. There were no significant differences between the nifedipine-treated and placebo groups in either the integrated TC or lesion induction ratio in either the 0.3% and 0.5% cholesterol-fed rabbits. This study demonstrates that nifedipine does not suppress atherogenesis in the intramural small coronary arteries of cholesterol-fed rabbits.

Granule-laden perivascular cells distributed around the fine vessels in brain of hypertensive rabbits fed a cholesterol diet were examined by electron microscopy. Perivenule granule-laden cells contained secondary lysosomes, residual bodies, Golgi vesicles, fusion vesicles, and vacuoles. In periarteriole granule-laden cells, secondary lysosomes and vacuoles were not prominent. Findings indicated that the granule-laden cell may be a histiocyte that appears during the vascular reaction to hypertension and hypercholesterolemia. This vascular reaction may occur more strongly in the veins than the arteries.

The aim of this study was to examine the suppressive effect of simvastatin on intramural coronary arterial lesions in cholesterol-fed rabbits. In one experiment, six groups of rabbits were fed laboratory chow alone or with added 0.1%, 0.2%, 0.3%, 0.5% or 1.0% cholesterol for 16 weeks. In another experiment, four groups of rabbits were fed a 0.5% cholesterol diet and treated with simvastatin at 1, 3, or 5 mg/kg/day or placebo. In each rabbit, the levels of serum total cholesterol (TC) were determined at 1-week intervals to calculate the integrated values. The lesion induction ratio was defined as the ratio of intramural coronary arteries 50-150 microm in diameter with arterial lipoidosis to the total number of arteries of the same diameter. In the two experiments, there were positive correlations between the lesion induction ratio and integrated TC (r=0.785, P<0.0001 and r=0.763, P<0.0001, respectively). The slopes of the regression lines for integrated TC obtained in the two experiments were similar, but the lesion induction ratio in the simvastatin-treated group was always lower, by about 14%, in comparison with that in the non-simvastatin-treated group. These findings suggest that simvastatin induces lesion reduction not only by reducing the levels of circulating cholesterol but also by directly suppressing the development of lipoidosis.