Antimitogenic effects of vasodilatory prostaglandins in coronary artery smooth muscle cells

Vasodilatory prostaglandins (PGI(2), PGE(2), PGE(1)) are known inhibitors o f proliferation of vascular smooth muscle cells (SMC) after stimulation wit h mitogenic factors. However endogenous prostaglandins do not prevent SMC p roliferation subsequent to vessel injury in vivo. Since vascular cells prod uce large amounts of antiproliferative prostaglandins, especially subsequen t to COX-2 expression, insufficient vascular PGI(2) formation is not likely to explain the failure of endogenous prostaglandins to prevent excessive S MC growth. In this paper we demonstrate a rapid development of tolerance to PGI(2) in SMC, resulting in diminished antiproliferative activity. These f indings may not only be relevant for the control of SMC growth by endogenou sly synthesized prostaglandins but also for clinical use of PGI(2) mimetics .