ENDOTHELIN ETB1 RECEPTOR-MEDIATED RELAXATION OF RABBIT BASILAR ARTERY

This study tests whether endothelin receptor agonist-induced relaxatio n of the cerebral vasculature is mediated via endothelin ET,, receptor activation. Sarafotoxin S6c, an endothelin ETB receptor agonist, rela xed rabbit basilar artery constricted with serotonin in situ. BQ788 (N -cis-2,6-dimethylpiperidinocarbonyl L-gamma-MeLeu-DTrp (COOCH3)-Nle), and RES-701-1 -Gly-Thr-Ala-Pro-Asp-Trp-Phe-Phe-Asn-Tyr-Tyr-Trp), endot helin ETB1/B2 and endothelin ETB1 receptor antagonists, respectively, prevented sarafotoxin S6c-induced relaxation. RES-701-1 was selective for the ETB1 receptor, as the endothelin-1 constriction elicited in th e presence of BQ610 (homopiperidenyl-CO-Leu-D-Trp (CHO)-D-Trp-OH), an endothelin ETA receptor antagonist, was enhanced by RES-701-1, and rel axed by BQ788. These results represent the first demonstration of the presence of endothelin ET,, receptors in the cerebral vasculature. (C) 1998 Elsevier Science B.V. All rights reserved.