ET(B) RECEPTORS PROMOTE PROLIFERATION AND MIGRATION OF ENDOTHELIAL-CELLS

We investigated endothelin-1 and -3 (ET-1, ET-3) effects on proliferat ion and migration of endothelial cells isolated from bovine adrenal ca pillaries (BACEs) and from human umbilical veins (HUVECs). Dose depend ent proliferation was produced by ET-1 and ET-3 in both cell lines, wi th maximal effects at 0.1 nM concentration. ET-1 and ET-3 also stimula ted BACE and HUVEC mobilization in a dose-dependent manner. The select ive agonist for the ET(B) receptor ET(16-21) showed the same effects a s ET-1 and ET-3 on proliferation and migration in both cell lines. The ET(B) receptor antagonist IRL 1038 (1 mu M) blocked the migration ind uced by both ET-3 and ET[16-21], whereas the ET(A) receptor antagonist BQ 123 (1 mu M) was ineffective. We conclude that endothelins, by fav oring endothelial cell growth and mobilization, can contribute to neov ascularization through an autocrine mechanism that requires ET(B) rece ptor activation.