Pravastatin Decreases Serum Lipids and Vascular Cholesterol Deposition in Watanabe Heritable Hyperlipidemic(WHHL) Rabbits.

Abstract

The effects of long term administration of pravastatin (a competitive inhibitor of hydroxymethylglutaryl CoA reductase) were assessed by measuring serum lipids and aortic and coronary atherosclerosis in Watanabe Heritable Hyperlipidemic (WHHL) rabbits. Six-month-old WHHL rabbits were given either 50 mg/kg/day of the drug or vehicle. The rabbits were sacrificed following 6 or 12 months of treatment and serum cholesterol and triglycerides and aortic cholesterol and hydroxyproline were measured. Atherosclerotic plaques in the aorta and coronary arteries were quantified with morphometric methods. Mean serum cholesterol +/- SEM (n) in the control vs. pravastatin groups after 6 months were: 535 +/- 34 (11) vs. 411 +/- 22 (12) (p less than 0.005) and after 12 months 458 +/- 43 (9) vs. 309 +/- 29 mg/dl (12) (p less than 0.005). In the pravastatin group, percent aortic area covered with plaque and aortic cholesterol content were reduced 35% (ns) and 55% (p less than 0.05) at 6 months, and 26% (ns) and 44% (ns) at 12 months, respectively. Little difference was found in serum triglycerides and aortic hydroxyproline in the 2 groups. There was strong correlation of serum cholesterol with aortic cholesterol content (r = 0.61, p less than 0.003) and with the percent aortic plaque area (r = 0.67, p less than 0.001), at 12 months. Morphometric analysis of wall thickness and lumen area of major coronary arteries revealed no significant differences in the 2 groups. In conclusion, pravastatin effectively lowered the serum cholesterol level in an animal model defective in low density lipoprotein receptors; this reduction was strongly correlated with amelioration of such atherosclerotic processes as lipid deposition and plaque formation.