Combination treatment with troglitazone, an insulin action enhancer, and pravastatin, an inhibitor of HMG-CoA reductase, shows a synergistic effect on atherosclerosis of WHHL rabbits.
We examined whether improving insulin resistance augments the antiatherosclerotic effect of LDL reduction. Since WHHL rabbits show hyperinsulinemia and insulin resistance, we administered troglitazone (100 mg/kg), an insulin action enhancer, pravastatin sodium (50 mg/kg), an HMG CoA reductase inhibitor, and a combination of both drugs to 2-month-old WHHL rabbits for 32 weeks. As compared to the control, total cholesterol levels in the plasma and LDL were decreased significantly by 20% in the pravastatin and combination groups. Basal immunoreactive insulin levels and insulin index were decreased significantly by approximately 50% in the troglitazone and combination groups. Surface lesion area of atherosclerosis on the thoracic aorta was decreased significantly by 36% in the combination group and was less in the troglitazone group. Coronary atherosclerosis was decreased significantly by 39% in the combination group and was less in the pravastatin and troglitazone groups. The collagen content in the plaques was decreased in the troglitezone and combination groups and the extracellular lipid deposits were decreased in the pravastatin and combination groups. The incidence and severity of xanthomata in the digital joints were also decreased significantly in the three treated groups. In conclusion, the antiatherogenic effect of the combination treatment is stronger than that of the monotherapy.
Institute for Experimental Animals, Kobe University School of Medicine, Japan.
M
M
Shiomi
T
T
Ito
T
T
Tsukada
Y
Y
Tsujita
H
H
Horikoshi
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D001786:Blood Glucose / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood; D002839:Chromans / Q000627:therapeutic use*; D003331:Coronary Vessels / Q000473:pathology; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D005951:Glucose Tolerance Test; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006946:Hyperinsulinism / Q000097:blood / Q000150:complications / Q000188:drug therapy; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D008297:Male; D017035:Pravastatin / Q000627:therapeutic use*; D011817:Rabbits; D013844:Thiazoles / Q000627:therapeutic use*; D045162:Thiazolidinediones; D000077288:Troglitazone; D014973:Xanthomatosis / Q000097:blood / Q000150:complications / Q000517:prevention & control
D001786:Blood Glucose; D008078:Cholesterol, LDL; D002839:Chromans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone; D017035:Pravastatin