The trapidil derivative AR 12456 protects against serum hyperlipidemia in guinea pigs

The administration of the trapidil derivative AR 12465 (5 mg/kg body weight) intraperitoneally to hypercholesterolemic guinea pigs caused a stronger reduction in serum total cholesterol (TC) than trapidil (20 mg/kg, i.p.) or a vehicle injection (saline with 5% ethanol i.p.). The stronger reduction of TC is caused by a lower level in the sum of all beta-migrating lipoproteins and an enhanced level of high-density lipoprotein. The levels of free and esterified cholesterol were not changed in kidney and left cardiac ventricle, but significantly enhanced (P less than 0.05) in the liver of all groups fed a cholesterol-rich diet. The elevation in liver cholesterol was higher in the group treated with AR 12456 than in the group treated with trapidil or with vehicle. The treatment with AR 12456 diminished the ratio TXB2/6-keto-PGF1 alpha for the capacity of aorta to form these prostanoids. In conclusion, our data show that AR 12456 has a strong antilipidemic action in guinea pigs fed a cholesterol-rich diet.