Effect of lacidipine on fatty and proliferative lesions induced in hypercholesterolaemic rabbits

1. The in vivo antiatherogenic activity of the calcium antagonist, lacidipine, was investigated in two different types of atherosclerotic lesions (proliferative and fatty lesions) induced in rabbits. 2. The proliferative lesion was obtained by positioning a hollow silastic collar around one carotid artery, while aortic fatty lesions were induced by cholesterol feeding. Cholesterol (1%) and lacidipine (1, 3, and 10 mg kg^-1) were given daily mixed with standard diet for 8 weeks to White New Zealand rabbits. The intimal hyperplasia (proliferative lesion) was induced 6 weeks after dietary and drug treatment started. 3. The neointimal formation was determined by measuring cross sectional thickness of intimal (I) and medial (M) tissue of fixed arteries. In untreated animals (n = 5), 14 days after collar positioning an intimal hyperplasia was clearly detectable: the arteries with no collar (sham) showed an I/M tissue ratio of 0.03 ± 0.02, whereas in the carotid with collar the ratio was 0.62 ± 0.12. In lacidipine-treated animals a significant and dose-dependent effect on proliferative lesions at all three doses tested, was observed. I/M ratios were 0.47 ± 0.02, 0.40 ± 0.09, 0.32 ± 0.02 for doses 1, 3, and 10 mg kg^-1 day^-1, respectively (P <0.05). 4. The fatty lesion extent was significantly reduced by lacidipine at the 10 mg kg^-1 day^-1 dose, although a trend was also observed with lower dosage. 5. These results suggest a direct antiatherosclerotic effect of lacidipine, independent of modulation of risk factors such as hypercholesterolaemia and/or hypertension. Furthermore, the proliferative lesions are apparently more sensitive to lacidipine than are lipid-rich lesions.