Failure of a slow channel calcium antagonist, verapamil, to retard atherosclerosis in the watanabe heritable hyperlipidemic rabbit: An animal model of familial hypercholesterolemia

Verapamil and other slow channel calcium antagonists have been reported to retard atherosclerosis in rabbits fed a high cholesterol diet. Because atherosclerosis in such a model may differ significantly from human atherosclerosis, experiments were conducted to prevent atherosclerosis with verapamil...

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Published in:Journal of the American College of Cardiology 1985-07, Vol.6 (1), p.141-144
Main Authors: Tilton, Gregory D., Buja, L. Maximilian, Bilheimer, David W., Apprill, Phillip, Ashton, Juliet, McNatt, Janice, Kita, Toru, Willerson, James T.
Format: Article
Language:English
Subjects:
Animals
Arteriosclerosis - pathology
Arteriosclerosis - prevention & control
Biological and medical sciences
Calcium Channel Blockers - therapeutic use
Disease Models, Animal
Female
General and cellular metabolism. Vitamins
Hyperlipidemias - complications
Hyperlipidemias - genetics
Hyperlipidemias - veterinary
Hyperlipoproteinemia Type II - complications
Male
Medical sciences
Pharmacology. Drug treatments
Rabbits
Verapamil - therapeutic use
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Summary:Verapamil and other slow channel calcium antagonists have been reported to retard atherosclerosis in rabbits fed a high cholesterol diet. Because atherosclerosis in such a model may differ significantly from human atherosclerosis, experiments were conducted to prevent atherosclerosis with verapamil in the Watanabe heritable hyperlipidemic (WHHL) rabbit, which is a genetic, metabolic and pathologic model of homozygous familial hypercholesterolemia. At 2 months of age, 23 WHHL rabbits were divided into two groups since earlier studies showed no macroscopic atherosclerosis at 2 months. Group A (n = 11) was fed standard rabbit chow for 6 months. Group B (n = 12) received oral verapamil (46 mg/kg per day) absorbed in the identical chow as fed to Group A and subcutaneous verapamil (0.25 mg/kg twice daily 6 days a week). In Group B, mean serum verapamil concentrations (± SEM) averaged 16.9 ± 1.9 ng/ml at 3 hours after subcutaneous injection. Sex ratios and serum cholesterol concentrations were the same in both groups. The percent of aortic surface area with visible plaque in Group A versus B was 49 ± 7 versus 43 ± 7%, respectively, of the entire aorta, and 61 ± 5 versus 65 ± 5%, respectively, of the proximal 3 cm of aorta (p = NS). Thus, verapamil did not suppress atherosclerosis in WHHL rabbits at serum drug levels greater than those reported to be effective in other models.
ISSN:0735-1097
1558-3597
DOI:10.1016/S0735-1097(85)80265-5