Suppression of established atherosclerosis and xanthomas in mature WHHL rabbits by keeping their serum cholesterol levels extremely low. Effect of pravastatin sodium in combination with cholestyramine.
We investigated the possibility that established atherosclerosis and xanthomas in mature WHHL rabbits could be suppressed or even regressed when their serum cholesterol levels were kept extremely low. Ten-month-old WHHL rabbits were divided into 3 groups, i.e. control rabbits, sacrificed at age 10 months, and placebo and treated rabbits, sacrificed at age 18 months. The treated rabbits were given pravastatin sodium (50 mg/kg/day), an HMG-CoA reductase inhibitor, in combination with cholestyramine (2% in diet), a bile acid sequestrant, for 36 weeks. The serum cholesterol levels and atherogenic lipoproteins in the treated group were markedly reduced, by about 60% (P less than 0.005 and P less than 0.001). Consequently, the degrees of both coronary and aortic atherosclerosis in the treated group were significantly reduced compared with the placebo group, and were almost the same as in the control group. The histopathological findings supported the above results. In addition, the incidence and degree of xanthomas in digital joints in the treated group were significantly reduced. These results suggest that established atherosclerosis and xanthomas in mature WHHL rabbits could be suppressed by keeping their serum cholesterol levels extremely low by the combination drug treatment.
Shiomi
M
M
Institute for Experimental Animals, Kobe University School of Medicine, Japan.
Ito
T
T
Watanabe
Y
Y
Tsujita
Y
Y
Kuroda
M
M
Arai
M
M
Fukami
M
M
Fukushige
J
J
Tamura
A
A
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001161:Arteriosclerosis / Q000097:blood / Q000188:drug therapy*; D002784:Cholesterol / Q000097:blood*; D002792:Cholestyramine Resin / Q000494:pharmacology / Q000627:therapeutic use*; D003327:Coronary Disease / Q000188:drug therapy; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D009281:Naphthalenes / Q000494:pharmacology / Q000627:therapeutic use*; D010743:Phospholipids / Q000097:blood; D017035:Pravastatin; D011817:Rabbits; D014280:Triglycerides / Q000097:blood; D014973:Xanthomatosis / Q000097:blood / Q000188:drug therapy*
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D009281:Naphthalenes; D010743:Phospholipids; D014280:Triglycerides; D002792:Cholestyramine Resin; D002784:Cholesterol; D017035:Pravastatin