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.
Szok
D
D
Department of Internal Medicine, Lund University Hospital, S-221 85 Lund, Sweden.
Hansen-Schwartz
J
J
Edvinsson
L
L
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D018999:Charybdotoxin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists / Q000378:metabolism*; D014160:Transducers, Pressure; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D001381:Azepines; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D007211:Indoles; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; D018999:Charybdotoxin; C079574:FR 139317