Regulatory effects of eicosanoids on thymidine uptake by vascular smooth muscle cells of rats

Abstract

To define the roles of eicosanoids in vascular smooth muscle cells(VSMC) growth, we examined the effects of exogenous eicosanoids on ( 3H)thymidine uptake by cultured VSMC of Wistar rats. Stable prostacyclin (PGI 2) analog, OP-41483, significantly decreased the incorporation of ( 3H)thymidine into deoxyribonucleic acid (DNA) of VSMC in a dose dependent manner from 10 −8 to 10 −4 M. Prostaglandin E 2 (PGSE 2) and PGD 2 ranging from 10 −8 to 10 −14 M also dose-dependently decreased the ( 3H)thymidine uptake by VSMC. In contrast, stable thromboxane A 2 analogm, STA 2, significantly increased the incorporation of ( 3H)thymidine into DNA in a dose dependent manner from 10 −8 to 10 −4 M. The dose response curve of STA 2 was shifted toward a lowered response when 10 −5 M PGI 2 analog, PGE 2 or PGD 2 was added in the culture medium. Thus, it is indicated that vasodepressor eicosanoids decrease the proliferation of VSMC, whereas vasoconstrictor TXA 2 enhances the VSMC growth. Vascular smooth muscle cells possibly autoregulate the cell proliferation through the eicosanoids generation.