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Effect of lacidipine on fatty and proliferative lesions induced in hypercholesterolaemic rabbits
Author(s) -
Soma M.R.,
Donetti E.,
Seregni R.,
Barberi L.,
Fumagalli R.,
Paoletti R.,
Catapano A.L.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15389.x
Subject(s) - lacidipine , lesion , medicine , intimal hyperplasia , hyperplasia , endocrinology , cholesterol , tunica intima , carotid arteries , antagonist , pathology , receptor , smooth muscle
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.