Anti-atherosclerotic activity of the calcium antagonist lacidipine in cholesterol-fed hamsters

We have investigated the activity of the calcium antagonist lacidipine in m ale hamsters fed an atherogenic diet containing 2% cholesterol and 5% butle r. Animals were examined at 14, 20 and 24 weeks of treatment. At 14 weeks, in hamsters fed the atherogenic diet and without lacidipine treatment, ther e were significant increases in serum levels of total cholesterol, triglyce rides and lipoproteins; these values were approximately similar at week 24. Lacidipine treatment at 0.3. 1.0 and 3.0 mg/kg/d did not affect levels of s erum cholesterol, triglycerides and lipoproteins. At 24 weeks, in hyperlipi demic hamsters fed the atherogenic diet, the area of the Fatty streak in th e aortic arch covered a mean area of 375 +/- 145 micron(2) x 100, which acc ounted for 2.7% of the total surface area of the aortic arch. In hamsters f ed the atherogenic diet and treated with lacidipine at 0.31 1.0 and 3.0 mg/ kg, at 24 weeks, the surface area of the aortic arch lesion was significant ly reduced by 41 to 71%. In the thoracic aorta at 24 weeks, in lacidipine-t reated animals, both the incidence and degree of severity of the lesions wa s reduced, the area of the fatty streak being lowered by 78 to 97% in compa rison with non-lacidipine-treated control animals. Ultrastructural examinat ion demonstrated that the early chanties in the aorta in hamsters fed the a therogenic diet involved the intima and smooth muscle cells; lacidipine tre atment reduced the severity of the intimal lesions significantly. With SEM, lacidipine administration was seen to reduce endothelial irregularity and the presence of crater-like lesions. At TEM, treatment with lacidipine redu ced the number of foam cells and the presence of liposomes in the subendoth elium. This investigation demonstrates that in the hyperlipidemic hamster, lacidipine treatment decreases atheromatous lesions without lowering serum lipids. It is suggested that lacidipine influences the atherogenic process by an unusual mechanism which may be related to a combination of both the l ong-lasting calcium antagonism of the drug and significant antioxidant acti vity. (C) 2000 Editions scientifiques et medicales Elsevier SAS.