In depth pharmacological characterization of endothelin B receptors in the rat middle cerebral artery

Whereas the endothelin A receptor is generally believed to mediate vasoconstriction; the endothelin B receptor seems elusive; both dilative and constrictive responses have been reported. Using the in vitro arteriograph, a method allowing compartmentalized study of vessel segments, segments of rat middle cerebral artery were cannulated with micropipettes, pressurized and luminally perfused. Vessel diameters were evaluated using a microscope equipped with an imaging system. Both intra- and extraluminal applications of endothelin-1 produced constriction. Intraluminal administration of a selective endothelin B receptor agonist sarafotoxin 6c in precontracted cerebral arteries and in the presence of the endothelin A receptor blocker FR139317 caused vasodilation in a concentration-dependent manner. Inhibition of nitric oxide synthase significantly reduced the dilation induced by sarafotoxin 6c, whereas inhibition of cyclooxygenase and endothelium-derived hyperpolarizing factor did not.