INHIBITION BY PROSTACYCLIN AND CARBACYCLINS OF ENDOTHELIN-INDUCED DNA-SYNTHESIS IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS

Effects of prostacyclin and carbacyclins on endothelin-induced DNA synthesis were investigated in vascular smooth muscle cells. DNA synthesis was estimated by [H-3]thymidine incorporation. Five carbacyclins used in this report were 5-{(1S, 5S, 6R, 7R)-7-hydroxy-6-[(E)-(S)-3-hydroxy-1-octenyl]bicyclo [3.3.0]oct-2-en-3-yl}pentanoic acid (TEI-7165), methyl 5-{(1S, 5S, 6R, 7R)-7-hydroxy-6-[(E)-(S)-3-hydroxy-1-octenyl]bicyclo[3.3.0]oct-2-en-3-yl}pentanoate (TEI-9090), 5-{(1S, 5S, 6R, 7R)-7-hydroxy-6-[(E)-(3S, 5S)-3-hydroxy-5-methyl-1-nonenyl]bicyclo[3.3.0]oct-2-en-3-yl}pentanoic acid (TEI-9063), methyl 5-{(1S, 5S, 6R, 7R)-7-hydroxy-6-[(E)-(3S, 5S)-3-hydroxy-5-methyl-1-nonenyl]bicyclo[3.3.0]oct-2-en-3-yl}pentanoate (TEI-1324), 5-{(1S, 5S, 6R, 7R)-7-hydroxy-6-[(E)-(S)-4-hydroxy-4-methyl-1-octenyl]bicyclo[3.3.0]oct-2-en-3-yl} pentanoic acid (TEI-3356). Prostacyclin and the carbacyclins inhibited the endothelin-induced DNA synthesis within the nanomolar range. These results suggest that prostacyclin and carbacyclins are possibly effective in inhibiting the proliferation of vascular smooth muscle cells under some situations in vivo.