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In vitro inhibition of arterial myocyte growth and stimulation of low density lipoprotein metabolism by SIM 6080, a new calcium antagonist.

Authors
  • Bernini, F
  • Fantoni, M
  • Corsini, A
  • Fumagalli, R
Type
Published Article
Journal
Pharmacological research
Publication Date
Jan 01, 1990
Volume
22
Issue
1
Pages
27–35
Identifiers
PMID: 2330336
Source
Medline
License
Unknown

Abstract

We have investigated the in vitro effect of the new calcium antagonist SIM 6080 on proliferation of rat aortic smooth muscle cells and on LDL receptor-mediated catabolism in human fibroblasts. Verapamil was used as the reference compound. SIM 6080 inhibited the proliferation of rat aortic myocytes in concentrations ranging between 1 and 20 microM. The inhibition, evaluated as cell number and nuclear incorporation of [3H]thymidine, was dose and time dependent; the cell doubling time increased with drug concentrations up to 69 h versus 20 h for controls. Similar results on both LDL pathway and smooth muscle cell proliferation were achieved with verapamil, but higher concentrations were needed. The specific uptake and degradation of 125I-LDL was evaluated in human fibroblasts after 48 h incubation with SIM 6080 (1-10 microM). The compound dose dependently enhanced the receptor-mediated 125I-LDL uptake, with a fourfold increase as a maximal effect (10 microM); LDL degradation was less sensitive to the drug. The present results provide evidence that the new calcium antagonist SIM 6080 interferes in vitro with processes involved in atherogenesis.

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