ETB receptors promote proliferation and migration of endothelial cells.

We investigated endothelin-1 and -3 (ET-1, ET-3) effects on proliferation and migration of endothelial cells isolated from bovine adrenal capillaries (BACEs) and from human umbilical veins (HUVECs). Dose-dependent proliferation was produced by ET-1 and ET-3 in both cell lines, with maximal effects at 0.1 nM concentration. ET-1 and ET-3 also stimulated BACE and HUVEC mobilization in a dose-dependent manner. The selective agonist for the ETB receptor ET(16-21) showed the same effects as ET-1 and ET-3 on proliferation and migration in both cell lines. The ETB receptor antagonist IRL 1038 (1 microM) blocked the migration induced by both ET-3 and ET[16-21], whereas the ETA receptor antagonist BQ 123 (1 microM) was ineffective. We conclude that endothelins, by favoring endothelial cell growth and mobilization, can contribute to neovascularization through an autocrine mechanism that requires ETB receptor activation.