INVITRO INHIBITION OF ARTERIAL MYOCYTE GROWTH AND STIMULATION OF LOW-DENSITY-LIPOPROTEIN METABOLISM BY SIM-6080, A NEW CALCIUM-ANTAGONISTS

We have investigated thein 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, μm. 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 of125I-LDL was evaluated in human fibroblasts after 48 h incubation with SIM 6080 (1-10 μm). The compound dose dependently enhanced the receptor-mediated125I-LDL uptake, with a fourfold increase as a maximal effect (10 μm); LDL degradation was less sensitive to the drug. The present results provide evidence that the new calcium antagonist SIM 6080 interferesin vitro with processes involved in atherogenesis. © 1990 The Italian Pharmacological Society.