EFFECT OF LACIDIPINE ON FATTY AND PROLIFERATIVE LESIONS INDUCED IN HYPERCHOLESTEROLEMIC RABBITS

1 The in vivo antiatherogenic activity of the calcium antagonist, laci dipine, was investigated in two different types of atherosclerotic les ions (proliferative and fatty lesions) induced in rabbits. 2 The proli ferative lesion was obtained by positioning a hollow silastic collar a round one carotid artery, while aortic fatty lesions were induced by c holesterol feeding. Cholesterol (1%) and lacidipine (1, 3, and 10 mg k g(-1)) were given daily mixed with standard diet for 8 weeks to White New Zealand rabbits. The intimal hyperplasia (proliferative lesion) wa s induced 6 weeks after dietary and drug treatment started. 3 The neoi ntimal 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 hyperplas ia was clearly detectable: the arteries with no collar (sham) showed a n I/M tissue ratio of 0.03 +/- 0.02, whereas in the carotid with colla r the ratio was 0.62 +/- 0.12. In lacidipine-treated animals a signifi cant and dose-dependent effect on proliferative lesions at all three d oses tested, was observed. I/M ratios were 0.47 +/- 0.02, 0.40 +/- 0.0 9, 0.32 +/- 0.02 for doses 1, 3, and 10 mg kg(-1) day(-1), respectivel y (P < 0.05). 4 The fatty lesion extent was significantly reduced by l acidipine at the 10 mg kg(-1) day(-1) dose, although a trend was also observed with lower dosage. 5 These results suggest a direct antiather osclerotic effect of lacidipine, independent of modulation of risk fac tors such as hypercholesterolaemia and/or hypertension. Furthermore th e proliferative lesions are apparently more sensitive to lacidipine th an are lipid-rich lesions.