Influence of the trapidil derivative AR 12463 on serum and tissue lipids and development of aortic lesions during experimental atherosclerosis in rabbits

Abstract

Daily administration of the trapidil derivative AR 12463 (20 mg/kg body weight i.p.) to cholesterol-fed rabbits diminished statistically significantly the increase in serum total cholesterol. After 8 weeks of treatment all measured lipoprotein fractions were significantly lower in animals treated with AR 12463 (group 3) compared with the values of the untreated control (group 1) or vehicle-treated group (group 2). The reduction of serum levels was associated with statistically significantly reduced levels of cholesterol esters in kidney, liver and aorta. The levels of free cholesterol in the liver of group 3 animals were statistically significantly lower compared with the levels in the two other groups, whereas in kidney and aortas the levels of free cholesterol remained unchanged under the influence of AR 12463. The area of aorta covered with fatty streaks was significantly smaller in group 3 versus group 1. The results of this study indicate that treatment of rabbits with AR 12463 while feeding a cholesterol-rich diet prevents hypercholesterolemia as well as the cholesterol incorporation into tissues. The mode of action of AR 12463 on serum and tissue lipids as well as on the development of atherosclerosis is discussed.