Background: Proliferation of vascular smooth muscle cells (VSMC) in the intima of arteries has been viewed as an important mechanism in atherogenesis. Oxidized low-density lipoprotein (oxLDL) can stimulate VSMC growth. Endothelin appears to serve as a mitogen for vascular smooth muscle cells. There is evidence suggesting a role for endothelin and its receptors in atherogenesis.Method: Aortic rabbit SMC were grown in IMDM containing 20% and then 0.5% newborn calf serum for 72 hours. Then cells were (1) incubated with different concentrations of LDL or oxLDL (oxidation of LDL was induced by incubation with Cu + + ) for 24 hrs, and (2) pretreated with different concentrations of selective nonpeptide ET A antagonist BMS-182874 followed by incubated with 10 μ g/ml oxLDL for 24 hrs. Cell proliferation was measured by non-radioactive MTS absorbance at 490 nm. ET A mRNA expression levels of VSMC incubated with BMS-182874 and/or oxLDL were also analyzed by Northern blot.Result: Low levels of oxLDL had significantly proliferative effect on VSMC, while high levels of which had cytotoxic effect. BMS-182874 significantly inhibited the proliferative response of VSMC evoked by oxLDL. OxLDL increased ET A mRNA expression levels of VSMC. BMS-182874 significantly reduced ET A mRNA expression stimulated by oxLDL.Conclusion: The results suggest that ET A receptor may be involved in atherogenesis. Selective non-peptide ET A antagonist BMS-182874 may potentially have clinical implication.