Anti-Atherosclerotic Effects of Probucol on Rabbits Differ between Fast Growers and Slow Growers

抄録

The anti-atherosclerotic effect of probucol was tested on weaned male New Zealand white rabbits. The rabbits, weighing 2kg, were first fed regular rabbit food ad libitum; and when their weight reached 3kg, they were placed on one of the following diets for 10 weeks: 1% cholesterol and 1% probucol rabbit food diet, or 1% cholesterol and regular rabbit food diet. At the end of the experiment we found that the presence of probucol in the diet reduced the level of plasma cholesterol and increased the resistance of low density lipoprotein to oxidation, whereas the drug had no significant beneficial effect of reducing the area of the aorta occupied by atherosclerotic plaques. When the data were probed further, it became apparent that the area of atherosclerotic plaques of the probucol/cholesterol-fed rabbit group was bimodal in distribution. In one subgroup of these rabbits, whose body weight reached 3kg between 6 and 8 weeks (fast grower) during the conditioning period, the area of atherosclerotic plaques (91.0±1.8% of total aortic surface) was the same as that of the cholesterol-fed fast growers (81.8±8%). In the other subgroup of rabbits, whose body weight reached 3kg between 10 and 11 weeks (slow grower) during the conditioning period, the area of atherosclerotic plaques (37.6±6.2%) was significantly (p<0.05) less than that of the cholesterol-fed slow growers (66.4±11.1%). In the comparison of the fast and slow growers on the probucol diet, the rate of weight gain was the only significant difference found. These observations suggest that the anti-atherosclerotic effect of probucol depends upon the rate of weight gain and that the effect may be mediated by an unknown mechanism.