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

Abstract

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-') 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-' day-', respectively (P< 0.05).4 The fatty lesion extent was significantly reduced by lacidipine at the 10 mg kg-' day' 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.

Different relation between 24-h blood pressure and distensibility at different peripheral arteries. Data from the European Lacidipine Study on Atherosclerosis (ELSA)

“…Second, the inverse relationship between CA distensibility and 24-h BP did not usually extend to diastolic values. This adds mechanistic evidence to the conclusion of several studies that SBP may be a better predictor of cardiovascular disease than DBP [29][30][31][32][33], because arterial stiffening increases the mechanical effect of intravascular pressure on the vessel wall, thereby favouring atherosclerosis [31,34]. Third, CA distensibility showed an inverse relationship with SBP variability.…”

Effects of lacidipine on vascular responses in patients with coronary artery disease

“…The antiatherosclerotic action of lacidipine was reproduced in many in vivo and in vitro studies. It includes an improvement of endothelial dysfunction and permeability, a decrease in smooth muscle cell proliferation and oxidation of low-density lipoproteins, and a reduction in adhesion molecule (ICAM-1, VCAM-1, and E-selectin) expression in tumor necrosis factor-a-stimulated endothelial cells [12][13][14][15]. Furthermore, its antioxidant effect is most strongly expressed as compared to other calcium channel blockers [20].…”

“…Its antiatherosclerotic effects include inhibition of fatty streak formation, reduction of cellular adhesion molecule expression, antioxidant effects, and improving endothelial dysfunction in hypertensive patients [12][13][14][15].…”

Calcium Antagonist Lacidipine Slows Down Progression of Asymptomatic Carotid Atherosclerosis

“…1 Among calcium antagonists, highly lipophilic, antioxidant, long-acting dihydropyridines such as lacidipine 2,3 were found to be particularly effective in experimental models of atherosclerosis. 4,5 B-mode ultrasound examination of the carotid arteries with measurement of intima-media thickness (IMT) has been used as a measure of asymptomatic atherosclerosis progression. 6 Three randomized trials of antihypertensive therapy showed smaller progression or greater regression of carotid lesions in patients treated with a calcium antagonist rather than a diuretic, [7][8][9] but the changes were small and the trials had limited power to detect these differences.…”