The role of ET(B) receptors in normotensive and hypertensive rats as revealed by the non-peptide selective ET(B) receptor antagonist Ro 46-8443

We used Ro 46-8443, non-peptidic antagonist selective of endothelin ET(B) receptors, to study the role of ET(B) receptors in rat hypertension models. In normotensive rats, Ro 46-8443 decreased blood pressure, but in SHR and DOCA rats, it induced a presser effect, due to blockade of ET(B)-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 presser but depressor effect. Thus, in DOCA rats and SHR, Ro 46-8443 reveals a predominant influence of endothelial 'vasorelaxant' ET(B) receptors, while in normotensive rats the prevailing role of ET(B) receptors seems to be in mediating a vasoconstrictor tone.