Hypercholesterolemia in ExHC rats and lipid-lowering drug: a screening method for new hypocholesterolemic agents.

The ExHC rat strain which was selected and bred from the Sprague-Dawley strain, develops severe hypercholesterolemia and is liable to aortic lipid deposition when the rats are fed an atherogenic diet. After only 4 days on the atherogenic diet, hypercholesterolemia was induced in these ExHC rats. Following a study of gel-filtration and SDS-disc electrophoresis, significant increases of broad-LDL (beta-VLDL) and of apo E and apo B were noted. On the other hand, plasma HDL and its major apolipoprotein, apo A-I, showed decreases. All these changes might be responsible for the future induction of aortic lipid deposition. A screening method for new hypocholesterolemic agents which takes advantage of these ExHC rat characteristics has been set up; it involves the evaluation of cholesterol lowering and HDL increasing effects by the determination of plasma cholesterol and by radioimmunoassay of apo A-I, respectively. Although clofibrate (100 mg/kg body weight) reduced plasma cholesterol levels significantly, there was no apo A-I increasing effect.