Proliferation of vascular smooth muscle cells(VSMC) is a critical event in the development of atherosclerosis. Endothelin-1(ET-1), a vasoconstrictor peptide produced by endothelial cells and VSMC, might play a role in vascular remodeling. To investigate the proposed 'mitogenic' potential of ET-1, we examined the effects of ET-1 on the proliferation if cultured porcine aortic VSMC and on the potential synergism with platelet-derived growth factor(PDGF).

VSMC were obtained from porcine aorta and cultured in Dulbecco's modified Eagle medium supplmented with 10% fetal bovine serum(FBS). VSMC grown subconfluently in 12-well plate were stimulated by ET-1, PDGF, and ET-1 & PDGF and DNA synthesis was determined as the uptake of ³H-thymidine into cell cultures. We also examined the effects of BQ123, a selective ET_A receptor antagonist, and N^G-methyl-L-arginine(NMLA), a nitric oxide synthase (NOS) inhibitor.

ET-1 elicited a 2.5-fold increase of cultured VSMC DNA synthesis, comparing with basal medium, and PDGF elicited a 4.8-fold increase, whereas ET-1 and PDGF elicited a 8.8-fold increase, showing synergistic effect. Proliferative activity of ET-1 on VSMC was blocked(39%) by BQ123, however, the synergistic effect of ET-1 and PDGF was not blocked by BQ123. The synergistic effect of ET-1 and PDGF was increased when co-stimulated with NMLA.

ET-1 is a co-mitogen for VSMC from porcine aorta, whose proliferative activity requires serum or other growth factors such as PDGF for its maximal activity. The proliferative activity of ET-1 is considered to be transduced partly by selective activation of the ET_A receptor, however, the synergistic effect of of ET-1 and PDGF is to be stimulated by non-ET_A receptor.