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

M. R. Soma, E. Donetti, R. Seregni, L. Barberi, R. Fumagalli, R. Paoletti, A. L. Catapano

Research output: Contribution to journalArticle

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-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.

Original languageEnglish
Pages (from-to)215-219
Number of pages5
JournalBritish Journal of Pharmacology
Volume118
Issue number2
Publication statusPublished - 1996

Fingerprint

Tunica Intima
Rabbits
Hyperplasia
Arteries
Cholesterol
Hypercholesterolemia
Carotid Arteries
lacidipine
Diet
Hypertension
Calcium
Lipids
Pharmaceutical Preparations

Keywords

  • Animal model
  • Atherosclerosis
  • Calcium antagonists
  • Fatty lesion
  • Lacidipine
  • Proliferative lesion
  • Smooth muscle cell proliferation

ASJC Scopus subject areas

  • Pharmacology

Cite this

Soma, M. R., Donetti, E., Seregni, R., Barberi, L., Fumagalli, R., Paoletti, R., & Catapano, A. L. (1996). Effect of lacidipine on fatty and proliferative lesions induced in hypercholesterolaemic rabbits. British Journal of Pharmacology, 118(2), 215-219.

Effect of lacidipine on fatty and proliferative lesions induced in hypercholesterolaemic rabbits. / Soma, M. R.; Donetti, E.; Seregni, R.; Barberi, L.; Fumagalli, R.; Paoletti, R.; Catapano, A. L.

In: British Journal of Pharmacology, Vol. 118, No. 2, 1996, p. 215-219.

Research output: Contribution to journalArticle

Soma, MR, Donetti, E, Seregni, R, Barberi, L, Fumagalli, R, Paoletti, R & Catapano, AL 1996, 'Effect of lacidipine on fatty and proliferative lesions induced in hypercholesterolaemic rabbits', British Journal of Pharmacology, vol. 118, no. 2, pp. 215-219.
Soma MR, Donetti E, Seregni R, Barberi L, Fumagalli R, Paoletti R et al. Effect of lacidipine on fatty and proliferative lesions induced in hypercholesterolaemic rabbits. British Journal of Pharmacology. 1996;118(2):215-219.
Soma, M. R. ; Donetti, E. ; Seregni, R. ; Barberi, L. ; Fumagalli, R. ; Paoletti, R. ; Catapano, A. L. / Effect of lacidipine on fatty and proliferative lesions induced in hypercholesterolaemic rabbits. In: British Journal of Pharmacology. 1996 ; Vol. 118, No. 2. pp. 215-219.
@article{a91c10f94fcc4eb3a43fce4dc9e2b875,
title = "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-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.",
keywords = "Animal model, Atherosclerosis, Calcium antagonists, Fatty lesion, Lacidipine, Proliferative lesion, Smooth muscle cell proliferation",
author = "Soma, {M. R.} and E. Donetti and R. Seregni and L. Barberi and R. Fumagalli and R. Paoletti and Catapano, {A. L.}",
year = "1996",
language = "English",
volume = "118",
pages = "215--219",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Effect of lacidipine on fatty and proliferative lesions induced in hypercholesterolaemic rabbits

AU - Soma, M. R.

AU - Donetti, E.

AU - Seregni, R.

AU - Barberi, L.

AU - Fumagalli, R.

AU - Paoletti, R.

AU - Catapano, A. L.

PY - 1996

Y1 - 1996

N2 - 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.

AB - 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.

KW - Animal model

KW - Atherosclerosis

KW - Calcium antagonists

KW - Fatty lesion

KW - Lacidipine

KW - Proliferative lesion

KW - Smooth muscle cell proliferation

UR - http://www.scopus.com/inward/record.url?scp=0029874968&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029874968&partnerID=8YFLogxK

M3 - Article

C2 - 8735617

AN - SCOPUS:0029874968

VL - 118

SP - 215

EP - 219

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 2

ER -