Inhibition by cardiac natriuretic peptides of rat vascular endothelial cell migration

Vascular endothelial cell migration is proposed to be an important process in the initiation and progression of atherosclerosis. We designed the present study to examine the effects of atrial and brain natriuretic peptides on fetal calf serum-stimulated migration of cultured rat aortic endothelial cells using Boyden's chamber method. Fetal calf serum clearly stimulated migration in a concentration- and time-dependent manner. Rat atrial natriuretic peptide-(1-28) and rat brain natriuretic peptide-45, which are the major circulating forms of atrial and brain natriuretic peptides in rats, inhibited fetal calf serum-stimulated migration in a concentration-dependent manner between 10(-10) and 10(-6) mol/L. Such inhibition by these natriuretic peptides was paralleled by an increase in the cellular level of cGMP. The addition of a cGMP analogue 8-bromo-cGMP, significantly inhibited fetal calf serum-stimulated migration in a concentration-dependent manner between 10(-7) and 10(-3) mol/L. Rat atrial natriuretic peptide-(5-25) was much less effective than atrial natriuretic peptide-(1-28) or rat brain natriuretic peptide-45 with respect to inhibiting migration and increasing cGMP levels. These results indicate that atrial and brain natriuretic peptides inhibit fetal calf serum-stimulated vascular endothelial cell migration, probably through a cGMP-dependent process.