ADRENOMEDULLIN AS A NOVEL ANTIMIGRATION FACTOR OF VASCULAR SMOOTH-MUSCLE CELLS

The present study investigated the effect of adrenomedullin, a novel v asorelaxant peptide, on the migration of cultured rat vascular smooth muscle cells (SMCs) by using the Boyden-chamber method. Fetal calf ser um (FCS) and platelet-derived growth factor (PDGF)-BB strongly stimula ted SMC migration. Adrenomedullin clearly inhibited SMC migration stim ulated with 5% and 10% FCS in a concentration-dependent manner. The mi gration induced by 10 and 25 ng/mL PDGF-BB was also inhibited by adren omedullin in a concentration-dependent manner. Inhibition by adrenomed ullin of FCS- and PDGF-induced SMC migration was paralleled by an incr ease in the cellular level of cAMP. In fact, the percent increase in c AMP level was strongly correlated with the percent decrease in migrati on activity of SMCs after treatment with adrenomedullin. S-Bromo cAMP, a cAMP analogue, reproduced the inhibition by adrenomedullin of FCS- and PDGF-induced SMC migration. An activator of adenylate cyclase, for skolin, also reduced FCS- and PDGF-induced SMC migration. These data i ndicate that adrenomedullin inhibits the migration of SMCs stimulated with FCS and PDGF, probably through a cAMP-dependent process. On the b asis of these results and the finding that adrenomedullin is synthesiz ed in and secreted from vascular endothelial cells, adrenomedullin may play a role as a local antimigration factor in some pathophysiologica l states.