We used Ro 46-8443, non-peptidic antagonist selective of endothelin ETB receptors, to study the role of ET8 receptors in rat hypertension models. In normotensive rats, Ro 46-8443 decreased blood pressure, but in SHR and DOCA rats, it induced a pressor effect, due to blockade of ETs-mediated release of nitric oxide since L-NAME prevented it. In rats rendered hypertensive by chronic L-NAME, Ro 46-8443 did not induce a pressor but depressor effect. Thus, in DOCA rats and SHR, Ro 46-8443 reveals a predominant influence of endothelial 'vasorelaxant' ETa receptors, while in normotensive rats the prevailing role of ETn receptors seems to be in mediating a vasoconstrictor tone.