Abstract
This study tests whether endothelin receptor agonist-induced relaxation of the cerebral vasculature is mediated via endothelin ET B1 receptor activation. Sarafotoxin S6c, an endothelin ET B receptor agonist, relaxed rabbit basilar artery constricted with serotonin in situ. BQ788 ( N- cis-2,6-dimethylpiperidinocarbonyl l-γ-MeLeu- d-Trp (COOCH 3)-Nle), and RES-701-1 (Gly-Asn-Trp-His-Gly-Thr-Ala-Pro-Asp-Trp-Phe-Phe-Asn-Tyr-Tyr-Trp), endothelin ET B1/B2 and endothelin ET B1 receptor antagonists, respectively, prevented sarafotoxin S6c-induced relaxation. RES-701-1 was selective for the ET B1 receptor, as the endothelin-1 constriction elicited in the presence of BQ610 (homopiperidenyl-CO-Leu- d-Trp (CHO)- d-Trp-OH), an endothelin ET A receptor antagonist, was enhanced by RES-701-1, and relaxed by BQ788. These results represent the first demonstration of the presence of endothelin ET B1 receptors in the cerebral vasculature.
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