Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Azepines / pharmacology
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Blood Pressure / drug effects
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Blood Pressure / physiology
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Charybdotoxin / pharmacology
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Dose-Response Relationship, Drug
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Endothelin Receptor Antagonists
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Endothelin-1 / metabolism*
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Endothelin-1 / pharmacology
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Enzyme Inhibitors / pharmacology
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Indoles / pharmacology
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Male
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Middle Cerebral Artery / drug effects
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Middle Cerebral Artery / metabolism*
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / metabolism*
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Rats
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Rats, Sprague-Dawley
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Receptor, Endothelin B
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Receptors, Endothelin / agonists
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Receptors, Endothelin / metabolism*
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Transducers, Pressure
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Vasoconstriction / drug effects
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Vasoconstriction / physiology*
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Vasoconstrictor Agents / pharmacology
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Viper Venoms / pharmacology
Substances
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Azepines
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Endothelin Receptor Antagonists
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Endothelin-1
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Enzyme Inhibitors
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Indoles
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Receptor, Endothelin B
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Receptors, Endothelin
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Vasoconstrictor Agents
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Viper Venoms
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sarafotoxins s6
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Charybdotoxin
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FR 139317