PROBUCOL TREATMENT ATTENUATES THE AORTIC ATHEROSCLEROSIS IN WATANABE HERITABLE HYPERLIPIDEMIC RABBITS

We examined the effect of probucol on the aortic atherosclerosis alrea dy developed in Watanabe heritable hyperlipidemic (WHHL) rabbits at th e initiation of treatment. In WHHL rabbits treated with probucol for 5 months from 8 months old, the lesion area in the aorta was significan tly (P<0.05) reduced when compared with that in untreated animals as w ell as animals at age 8 months. In contrast, plasma cholesterol levels in the probucol-treated group and untreated group during the experime nt were not significantly different. LDL prepared from rabbits receivi ng probucol for 5 months showed resistance to oxidation by copper ions . Plasma CETP activity was significantly (P<0.05) increased by probuco l treatment. An immunohistochemical study showed that macrophages were abundant in the atherosclerotic lesions of untreated rabbits whereas smooth muscle cells were predominant in lesions of probucol-treated ra bbits. These results suggest that the atherosclerotic lesion in WHHL r abbits can regress when treated by probucol and that the attenuation o f atherosclerosis in this animal involves effects of probucol other th an a decrease in plasma cholesterol, for example anti-oxidant activity . (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.