Combined treatment of probucol with diltiazem regresses atherosclerosis induced by 196 cholesterol diet in rabbit aorta.
To clarify whether probucol, an antioxidant, or diltiazem, a Ca2+ antagonist, favorably affect the regression of established atherosclerosis, rabbits were fed a 1% cholesterol diet for 10 weeks, then a standard diet for an additional 25 weeks (regression period). During the regression period, rabbits were grouped into a saline (S) group (n=8, 1 ml saline/d), a probucol (P) group (n=8, 1000 mg/d probucol), or a probucol and diltiazem (P+D) group (n=8, probucol 1000 mg/d in diet and diltiazem 30 mg/d). We measured cholesterol in serum, lipoprotein fractions, and serum triglyceride or phospholipid concentration and found no significant differences among the three groups at 10, 15, or 35 weeks. After 10 weeks of the atherogenic diet, the ratio of macroscopic atherosclerotic lesions in aortic intima rose to 36.6 + or - 5.6%. After the regression period, the S group developed more atherosclerotic lesions (48.6 + or - 6.4%). The P+D and P groups, however, had decreased scores of 24.3 + or - 5.5% (p<0.05 vs. S) and 32.3 + or - 5.6%, respectively. Moreover, these decreased scores were well correlated with the decrease in aortic tissue lipid compositions, but not the parameters for extracellular matrices. We concluded that P+D or P therapy might be effective in regressing established atherosclerosis by removing lipid contents but not extracellular matrices.