Prevention of progression of minimal coronary lesions with a calcium channel blocker

Waters, David D.; Lespérance, Jacques; Théroux, Pierre; Francetich, Marilyn; Reitman, Martha; Havel, Richard J.

doi:10.1016/0735-1097(90)92179-6

Cited by 8 publications

(2 citation statements)

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“…The in vitro effects of these drugs on processes which play a role in the development of atherosclerotic lesions might help in explaining these results. For instance, several calcium antagonists inhibit the migration of smooth muscle cells (SMC) (Nomoto et al, 1988), the uptake of lipids by macrophages (Daugherty et al, 1987;Stein & Stein, 1987;Schmitz et al, 1988;Bernini et al, 1991), and the production of collagen, elastin, and proteoglycans (Waters et al, 1990). However, few attempts have been made to relate these in vitro effects to the complex changes which occur in the vessel wall.…”

Section: Introductionmentioning

confidence: 99%

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

Soma

Donetti

Seregni

et al. 1996

British J Pharmacology

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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.

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Section: Introductionmentioning

confidence: 99%

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

Soma

Donetti

Seregni

et al. 1996

British J Pharmacology

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“…The in vitro effects of these drugs on processes which play a role in the development of atherosclerotic lesions might help in explaining these results (Bernini et al , 1989; Catapano et al , 1988; Lichtor et al , 1989). For instance, several calcium antagonists inhibit the migration of smooth muscle cells (SMC) (Nomoto et al , 1988), the uptake of lipids by macrophages (Daugherty et al , 1987; Bernini et al , 1991; Schmitz et al , 1988; Stein & Stein, 1987), and the production of collagen, elastin, and proteoglycans (Waters et al , 1990) and in several in vivo experiments the ‘antiatherosclerotic’ properties of Ca 2+ antagonists have been substantiated (Catapano, 1997). The question whether these effects can be extrapolated to human being however is still unsolved and studies on the beneficial effects of Ca 2+ antagonist on myocardial infarction morbility and mortality are so far negative (Cleland & Krikler, 1993).…”

Section: Introductionmentioning

confidence: 99%

Effect of lercanidipine and its (R)‐enantiomer on atherosclerotic lesions induced in hypercholesterolemic rabbits

Soma

Natali

Donetti

et al. 1998

British J Pharmacology

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1 The in vivo antiatherogenic activity of the calcium antagonist lercanidipine and its (R)-enantiomer was investigated in two dierent types of atherosclerotic lesions (hyperplastic and fatty-streak lesions) in rabbits. were given by subcutaneous injection for 10 weeks to White New Zealand rabbits, with cholesterol feeding beginning at week 2. The hyperplastic lesion was obtained by positioning a hollow silastic collar around one carotid artery, while aortic fatty streak lesions were induced by cholesterol feeding. In untreated animals (n=5), 14 days after collar positioning an intimal hyperplasia was clearly detectable: the arteries without collar showed a intima/media (I/M) ratio of 0.03+0.02, whereas in carotids with a collar the ratio was 2+0.42. In lercanidipine-treated animals a signi®cant and dose-dependent eect on intimal hyperplasia was observed. I/M ratios were 0.73+0.4, 0.42+0.1, 0.32+0.1 for 0.3, 1, and 3 mg kg 71 week 71, respectively (P50.05). The lercanidipine enantiomer (3 mg kg 71 week 71 ) was as eective as the racemate (0.41+0.11). Proliferation of smooth muscle cells, assessed by incorporation of BrdU into DNA, was reduced by about 50%, 70%, 85%, and 80% by lercanidipine (0.3, 1, and 3 mg kg 71 week 71) and its (R)-enantiomer, respectively. 3 The area of fatty-streaks in the aorta (n=11 ± 15) was signi®cantly reduced by lercanidipine (3 mg kg 71 week 71 , 16% vs 27%, P50.05), a trend was observed also with lower doses. When dierent segments of the aorta were considered (arch, thoracic, abdominal) a signi®cant and dose-dependent eect in the thoracic and abdominal aorta was observed also at lower doses. The (R)-enantiomer was as eective as lercanidipine. 4 These results suggest a direct antiatherosclerotic eect of lercanidipine, independent of modulation of risk factors such as hypercholesterolemia and/or hypertension as demonstrated by the absence of stereoselectivity.

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Concept of an antiatherosclerotic efficacy of calcium entry blockers

et al. 1992

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Animal experiments suggest an inhibitory effect of calcium entry blockers on arterial calcinosis and the formation of atherosclerotic plaques. Experiments with isolated tissues suggest various mechanisms for an antiatherosclerotic effect of calcium entry blockers. INTACT, the International Nifedipine Trial on Antiatherosclerotic Therapy, is the first study investigating, with a prospective, placebo-controlled, randomized, double-blind design, the influence of a calcium entry blocker (nifedipine 80 mg/day) on the progression of coronary atherosclerosis in patients with proven coronary artery disease. Study endpoints were changes of established coronary stenoses (diameter reduction greater than or equal to 20%), as well as the formation of new stenoses as documented by coronary angiography. Standardized coronary angiograms were taken before and after a treatment period of 3 years. The angiograms were quantitatively analyzed with the computer-assisted edge detection system CAAS. Of the 425 patients included in the study, 282 patients (134 on nifedipine and 148 on placebo) revealed no protocol violations. In the inclusion angiograms of these patients, 893 coronary stenoses were detected which were not significantly influenced in their development by nifedipine. However, 196 entirely new coronary lesions, 185 stenoses and 11 occlusions, were found in the follow-up angiograms. There were 78 lesions in 54 patients (40%) on nifedipine (0.58 new lesions/patient) and 118 lesions in 73 patients (49%; n.s.) on placebo (0.8 new lesions/patient; p = 0.031). In two other studies on the inhibiting effect of dihydropyridine calcium entry blockers on the progression of coronary artery disease in man defining angiographic endpoints, the drugs were also shown to reduce the number of newly formed significant coronary lesions. If further trials in man confirm a protective role of calcium entry blockers against the formation of atherosclerotic coronary lesions, a new strategy in the prevention of coronary artery disease has to be considered.

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Prevention of progression of minimal coronary lesions with a calcium channel blocker

Cited by 8 publications

References 0 publications

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

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

Effect of lercanidipine and its (R)‐enantiomer on atherosclerotic lesions induced in hypercholesterolemic rabbits

Concept of an antiatherosclerotic efficacy of calcium entry blockers

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