title: Endothelin receptor mediated constriction and dilatation in feline cerebral resistance arterioles in vivo.
abstract: The receptors mediating the cerebrovascular actions of endothelins have been examined in feline cerebral resistance arterioles in vivo. The adventitial microapplication of the endothelin ETA receptor antagonist BQ-123 (cyclo D-aspartate-D-tryptophan-L-leucine-D-valine-L-proline) (0.1-10 microM) per se had minimal effect on cerebral resistance arterioles examined. The adventitial microapplication of endothelin-1 (10 nM) elicited a marked vasoconstriction of cerebral resistance arterioles (-29.1 +/- 1.9% from pre-injection baseline). The endothelin-1 induced vasoconstriction was attenuated, in a dose dependent manner, by the adventitial co-application of BQ-123 and endothelin-1 (estimated IC50 0.7 microM). The adventitial microapplication of the endothelin ETB receptor agonist BQ-3020 N-acetyl[Ala11,Ala15]ET-1 (6-21)) (0.001-1 microM) effected a dose dependent vasodilatation (EC50 30 nM, maximum response 25 +/- 5% from pre-injection baseline). The magnitude of the vasodilatation elicited by BQ-3020 (100 nM and 1 microM) was dependent on the pre-injection calibre of the arterioles examined. The intracarotid infusion (via the lingual artery) of BQ-3020 (0.5-500 pmol/min) had no significant effect on the calibre of cerebral resistance arterioles. These results suggest that the peptide endothelin ETB receptor agonist fails to gain access to the cerebrovascular endothelin ETB receptors following its intraluminal administration. These investigations indicate that endothelin ETA receptors mediate vasoconstriction and endothelin ETB receptors mediate vasodilatation in feline cerebral resistance arterioles in vivo.
authors.affiliation: Wellcome Surgical Institute, University of Glasgow, Scotland, UK.
authors.forename: T R
authors.initials: TR
authors.lastname: Patel
authors.forename: M A
authors.initials: MA
authors.lastname: McAuley
authors.forename: J
authors.initials: J
authors.lastname: McCulloch
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000648:ultrastructure*; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D019332:Endothelin-1 / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology; D005260:Female; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000187:drug effects / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D019332:Endothelin-1; D016232:Endothelins; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; C075771:BQ 3020; C072247:cyclo(Trp-Asp-Pro-Val-Leu)